AU2015258729A1 - Antiperspirant deodorant cosmetic composition having dermo-calming action - Google Patents

Antiperspirant deodorant cosmetic composition having dermo-calming action Download PDF

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AU2015258729A1
AU2015258729A1 AU2015258729A AU2015258729A AU2015258729A1 AU 2015258729 A1 AU2015258729 A1 AU 2015258729A1 AU 2015258729 A AU2015258729 A AU 2015258729A AU 2015258729 A AU2015258729 A AU 2015258729A AU 2015258729 A1 AU2015258729 A1 AU 2015258729A1
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composition according
product
erythema
agent
application
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AU2015258729A
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Silvania ANGELINO DOS SANTOS TEODORO
Elisangela De Souza Costa
Selma NASCIMENTO
Joice SAVIETTO
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Natura Cosmeticos SA
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Natura Cosmeticos SA
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
    • A61K8/26—Aluminium; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/34—Alcohols
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/40—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
    • A61K8/42—Amides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/58—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing atoms other than carbon, hydrogen, halogen, oxygen, nitrogen, sulfur or phosphorus
    • A61K8/585—Organosilicon compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
    • A61K8/84—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds obtained by reactions otherwise than those involving only carbon-carbon unsaturated bonds
    • A61K8/86—Polyethers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q15/00—Anti-perspirants or body deodorants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/005—Preparations for sensitive skin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
    • A61K2800/59—Mixtures
    • A61K2800/592—Mixtures of compounds complementing their respective functions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/74—Biological properties of particular ingredients
    • A61K2800/75—Anti-irritant

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Birds (AREA)
  • Epidemiology (AREA)
  • Emergency Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Inorganic Chemistry (AREA)
  • Dermatology (AREA)
  • Cosmetics (AREA)

Abstract

The present invention relates to antiperspirant deodorant cosmetic compositions comprising 2-methyl-5-cyclohexylpentanol, aluminum hydrochloride, hydroxypropylic starch phosphate, pantenol, and cosmetically acceptable adjuvants. Said compositions exhibit deodorant and antiperspirant actions, sensorial emollient characteristics, and a protective film, and further provide a dermo-calming action on the skin for after- depilation use.

Description

WO 2015/172221 PCT/BR2015/050058 1
Specification of the Patent of invention for: “ANTIPERSPIRANT DEODORANT COSMETIC COMPOSITION HAVING DERMO-CALMING ACTION”
FIELD OF THE INVENTION 5 The present invention relates to antiperspirant deodorant cosmetic compositions with dermo-caiming action for after-depiiation sensitized skin, applicable in the cosmetic, hygiene and personal-care industry.
BACKGROUND OF THE INVENTION 10 Deodorants are intended for perfuming the body and, in general, they contain antimicrobial components, particularly antibacterial and antifungal, which eliminate bacteria and fungi that cause bad smell on the skin. Deodorants may be applied to armpits to perfume them and diminish the odors generated in this body region; however they do not prevent 15 perspiration.
Antiperspirants have the function of controlling the perspiration by inhibiting or reducing it, thus guaranteeing protection against sweat, besides having antimicrobial action, eliminating the microorganisms that cause bad smell. The antiperspirant action is due to the fact that this product 20 acts by forming a blocking film that prevent sweat from coming out, without causing damage to one’s health.
It is known that depilation, be it by wax, laser or nippers, induces cutaneous irritation in determined persons and body regions.
Among the measures which one should take with depilation are: 25 non-exposure to direct sunshine, skin cleaning, use of light and loose clothes, as well as attention to deodorants, creams and body oils used after the depilatory procedure. For this reason, care with the skin has become essential, although cutaneous irritations still occur, even with such care.
In this regard, the search for specific products for this purpose, 30 particularly for deodorants that provide relief of irritation caused on the skin, i.e., sensitized by depilation, becomes critical. Also, in addition to deodorants that relieve irritation, it becomes essential to develop products that group WO 2015/172221 2 PCT/BR2015/050058 deodorant characteristics to fight odor, antiperspirant for reducing sweat, and still that have a dermo-calming action on the skin. A few examples of prior-art documents related to the area of the present invention, particularly antiperspirant deodorants, are presented 5 hereinafter.
Patent application PI0924661-4, published on November 21, 2012, in the name of Symrise AG, relates to uj~cycle-hexyiaikan~1-ols, to the use of said compounds as antimicrobial agents for the treatment of odor on the body or for the preparation of an antimicrobial cosmetic or 10 pharmaceutical formulation. Said PI0924661-4 further describes antimicrobial formulations containing, for instance, 2-methyl-cyclohexylpentanol, However, said document does not mention or suggest the use of said active or formulations thereof as antiperspirant deodorants with dermo-calming action, especially for after-depilation sensitized skin. 15 US Patent 8,115,033, published on February 14, 2012, in the name of Symrise Ag relates to the chemical compound 3-{4-hydroxy~3-methoxyphenyl)-1 -(4-hydroxyphenyl)-1 -propanone, which is different from the chemical compound of the present invention called SymDeo® B125: 2-methyl-5-cydohexylpentanol. In the same way as the above-cited document, 20 Patent US 8,115,033 does not mention or suggest the use of the active presently described and claimed or its formulations as antiperspirant deodorants with dermo-calming action, or use on after-depilation sensitized skin. In addition, even if this were the case, this is an active ingredient that is not foreseen in the composition of the present invention. 25 US Patent US 6,172,016, published on January 9, 2001, in the name of Bush Boakes Allen Inc., is directed to the use of pentane derivatives as cosmetic ingredients. The difference with respect to the chemical compounds SymDeo of the present invention lies in the carbon to which the methyl radical is attached, which is the third one in the American patent, 30 namely: 3-methyl-5-cyclohexylpentanol. Again, this is a document that foresees a deodorant composition without the after-depilation calming benefit for sensitized skins. WO 2015/172221 3 PCT/BR2015/050058
Therefore, the need to develop antiperspirant deodorant formulations with dermo-calming action stiil remains, particularly for sensitized skins, which, in addition to the deodorant and antiperspirant properties, will exhibit emollient sensorial characteristics and a protective 5 film, and provide dermo-calming action on the skin. Such need is fully met with the composition of the present invention.
SUMMARY OF THE INVENTION
The present invention relates to antiperspirant deodorant cosmetic compositions with dermo-calming action, which comprise as active 10 ingredients, 2-methy!-5-cyciohexyipentanoi and aluminum hydrochloride, as well as commercially acceptable adjuvants, directed to application in the cosmetic, hygiene and body-care industry.
BRIEF DESCRIPTION OF THE FIGURES
Figure 1 refers to the result of treatment average as a function of 15 the test for instrumental evaluation of the effect of the composition of the invention (called 13-39540-03) versus control composition on erythema induced by the tape-stripping technique.
Figure 2 refers to the result of variation percentage in the average of the test for instrumental evaluation of the effect of the composition 20 of the present invention (called 13-39540-03) versus control composition on erythema induced by the tape stripping technique.
Figure 3 refers to the result of the average difference as a function of the time TO of the test for instrumental evaluation of the effect of the composition of the invention (called 13-39540-03) versus control 25 composition on erythema induced by the tape-stripping technique.
Figure 4 refers to the result of treatment average as a function of the time of the test for instrumental evaluation of the effect of the composition of the present invention (called 13-39540-04) versus control composition on erythema induced by the tape-stripping technique. 30 Figure 5 refers to the result of variation percentage in the average of the test for instrumental evaluation of the effect of the composition WO 2015/172221 4 PCT/BR2015/050058 of the invention (called 13-39540-04) versus control composition on erythema induced by the tape-stripping technique.
Figure 6 refers to the result of average difference as a function of the time TO of the test for instrumental evaluation of the effect of the 5 composition of the invention (called 13039540-04) versus control composition on erythema induced by the tape-stripping technique.
Figure 7 refers to the result of treatment average as a function of the time of the test for instrumental evaluation of the effect of the composition of the invention (called 13-39540-01) versus control composition on erythema 10 induced by the tape-stripping technique.
Figure 8 refers to the result of variation percentage in the average of the test for instrumental evaluation of the effect of the composition of the invention (called 13-39540-01) versus control composition on erythema induced by the tape-stripping technique. 15 Figure 9 refers to the result of average difference as a function of the time TO of the test for instrumental evaluation of the effect of the composition of the invention (called 13-39540-01) versus control composition on erythema induced by the tape-stripping technique.
Figure 10 refers to the result of treatment average as a function 20 of the time of the test for instrumental evaluation of the effect of the composition of the invention (called 13-39540-02) versus control composition on erythema induced by the tape-stripping technique.
Figure 11 refers to the result of variation percentage in the average of the test for instrumental evaluation of the effect of the composition 25 of the invention (called 13-39540-02) versus control composition on erythema induced by the tape-stripping technique.
Figure 12 refers to the result of average difference as a function of the time TO of the test for instrumental evaluation of the effect of the composition of the invention (called 13-39540-02) versus control composition 30 on erythema induced by the tape-stripping technique.
Figure 13 refers to the average value of the erythema (E) for the product and control evaluated as a function of the time referring to the test for WO 2015/172221 PCT/BR2015/050058 5 evaluation of the reduction of the erythema by using the composition of the invention (called NT1123-12-A).
Figure 14 refers to the average value of the reduction the erythema (%RE) for the product and control evaluated as a function of the 5 time referring to the test for evaluation of the reduction of erythema by using the composition of the invention (called NT1123-12-A).
Figure 15 refers to the average value of the intensity of the erythema (+a*) for the product and control evaluated referring to the test for evaluation of the reduction of erythema by using the composition of the 10 invention (called NT 1123-12-A).
Figure 16 refers to percentage of reduction of the intensity of the erythema (%RIE) as a function of the time referring to the test for evaluation of the reduction of erythema by using the composition of the invention (called NT1123-13-A). 15 Figure 17 refers to the result of treatment average as a function of the test for instrumental evaluation of the effect of the composition of the invention (called 12-33171-07) versus control composition on erythema induced by the tape-stripping technique.
Figure 18 refers to the result of variation percentage in the 20 average of the test for instrumental evaluation of the effect of the composition of the invention (called 12-33171-7) versus control composition on erythema induced by the tape-stripping technique.
Figure 19 refers to the result of average difference as a function of the time TO of the test for instrumental evaluation of the effect of the 25 composition of the invention (called 12-33171-07) versus control composition on erythema induced by the tape-stripping technique.
DETAILED DESCRIPTION OF THE INVENTION
The antiperspirant deodorant cosmetic compositions with dermo-calming action of the present invention comprise 2-methyl-5-30 cyclohexylpentanol and aluminum hydrochloride and derivatives thereof as active ingredients, as well as cosmetically acceptably adjuvants. WO 2015/172221 6 PCT/BR2015/050058
Said adjuvants suitable for the purposes of the cosmetic compositions of the invention are selected, for example, from the group consisting of demineralized water, oils, emulsifiers, preservatives, sequestrants (chelating agents), fragrance and others cosmetically 5 acceptable components. A few examples of inert adjuvants and constituents compatible with the properties of the compositions described herein and that, additionally, may be employed in the present cosmetic composition are given hereinafter - in a non-restrictive, but only demonstrative manner: 10 - Water: water is the base of a number of preferred embodiments of the cosmetic composition of the present invention, acting as a carrier for other components. The compositions of the present invention comprise water, preferably demineralized or distilled at a suitable percentage (q.s.p.) for reaching 100% of the formula, based on the total weight of the present 15 composition. Naturally, one may use other cosmetically acceptable carriers in the present invention; skin conditioning agent: pantenol; emollients: olus oil, stearylic PPG-15 ether, dicapryl carbonate, silicones, cyclometicone, dimeticonol, cyclopentasyloxane, hydrogenated 20 palm oil; antioxidant agents: butylated hydroxidetoluene (BHT), butyiated hydroxide anisol (BHA), among other; chelating agents: EDTA, among others; consistency agents: silica dimethyl sililate, magnesium silicate 25 (talc), ceresin wax, hydroxypropyl starch phosphate; and emulsifying agents: steareth-2, steareth-21, cetostearyl alcohol, cetearefh-20.
The composition according to the present invention may be present in different cosmetic forms as, for instance, and without any 30 limitation, in the form of roll-on or cream deodorant.
According to a preferred embodiment of the present invention, the deodorant cosmetic composition of the present invention comprises: WO 2015/172221 PCT/BR2015/050058 i 2-methyi-5-cyclohexyipentanol in an amount ranging from 0.1 to 1% by weight, preferably from 0.3 to 0.5%, more preferably 0.4% as a deodorant active ingredient; 50% solution of aluminum hydrochloride in an amount ranging 5 from 5.0 to 40% by weight, preferably from 10 to 35%, more preferably 30%, as an active ingredient and antiperspirant agent;
Pantenol in an amount ranging from 0.5 to 5% by weight, preferably from 0.8 to 3%, more preferably from 1 to 1.5% as a skin conditioning agent; 10 - BHT in an amount ranging from 0.1 to 0.5% by weight, preferably from 0.04 to 0.3%, more preferably 0.05% as an antioxidant agent; DMDM hydantoin in an amount ranging from 0.1 to 1% by weight, preferably from 0.3 to 0.8%, more preferably 0,6% as a preservative agent; 15 - EDTA in an amount ranging from 0.05 to 0.5% by weight, preferably from 0.08 to 0.2%, more preferably 0.1% as a chelating agent;
Silica dimethyl silicate, magnesium silicate (talc), ceresin wax, hydroxypropylic starch phosphate in an amount ranging from 0.05 to 6% by weight, preferably from 0.08 to 5%, more preferably from 0.15 to 4%, as a 20 consistency agent;
Olus soil, stearylic PPG-15 ether, hydrogenated palm oil, dicapryl carbonate, cyclomethicone silicones, dimethiconol, cyclopentasiloxane, in an amount ranging from 0.5 to 15% by weight, preferably from 0.8 to 10%, more preferably from 0.1 to 7% as emollients; and 25 - Steareth-2, steareth-21, cetostearyl alcohol, ceteareth-20 in an amount ranging from 0.5 to 15% by weight, preferably from 1.0 to 10%, more preferably from 1.1 to 9.5% as emulsifying agents.
The antiperspirant deodorant cosmetic composition with dermo-calming action of the present invention has a number of advantages and 30 desired characteristics with the ideal and balanced combination between its components, some of which are listed below: differentiated antiperspirant protection; WO 2015/172221 8 PCT/BR2015/050058 differentiated viscosity; differentiated hydration; protective film characteristic; differentiated softness; and 5 - dermo-calming action, particularly for sensitized skins.
The embodiments of the invention exemplified hereinafter are intended to illustrate, without limiting, the scope of their object. EXAMPLES: EXAMPLE 1 - THE COSMETIC COMPOSITION OF THE 10 PRESENT INVENTION IN ROLL-ON FORM (called 12-33171-07)
Table 1 below presents an example of formulation of the cosmetic composition according to the present invention in roll-on form. Table 1 Component Concentration (% by weight) Demineralized water 56.3 Aluminum hydrochloride (50% solution) 30.0 Olus oil 3.8 Steareth-2 3.0 Hydroxypropylic starch phosphate 1.5 Steareth-21 1.1 Stearylic PPG-15 ether 1.0 Perfume 1.0 Pantenol 1.0 DMDM hydantoin 0.6 2-methyl-5-cyclohexylpentanol 0.4 Silica dimethyl silicate 0.15 Disodium EDTA 0.1 BHT 0.05 EXAMPLE 2 - THE COSMETIC COMPOSITION OF THE 15 PRESENT INVENTION IN ROLL-ON FORM (called 13-39540-01) without olus oil)) WO 2015/172221 9 PCT/BR2015/050058
Table 2 below presents one more example of formulation of the cosmetic composition according to the present invention in roll-on form. Table 2 Component Concentration (wt.-%) Demineralized water 60.1 Aluminum hydrochloride (50% solution) 30.0 Steareth-2 3.0 Hydroxypropylic starch phosphate 1.5 Steareth-21 1.1 Stearylic PPG-15 ether 1.0 Perfume 1.0 Pantenol 1.0 DMDM hidantoin 0.6 2-methyl-5-cyclohexylpentanol 0.4 Silica dimethyl silicate 0.15 Disodium EDTA 0.1 BHT 0.05 EXAMPLE 3 - THE COMPOSITION OF THE PRESENT INVENTION IN ROLL-ON FORM (called 13-39540-02 (with palm oil)) Table 3 below presents one more example of formulation of the cosmetic composition according to the present invention in roll-on form. Table 3 Component Concentration (wt.-%) Demineralized water 59.1 Aluminum hydrochloride (50% solution) 30.0 Steareth-2 3.0 Hydroxypropylic starch phosphate 1.5 Steareth-21 1.1 Stearylic PPG-15 ether 1.0 Hydrogenated palm oil 1.0 Perfume 1.0 Pantenol 1.0 WO 2015/172221 10 PCT/BR2015/050058 DMDM hydantoin 0.6 2-methy!-5-cyc!ohexy!penlano! 0.4 Silica dimethyl silicate 0.15 Disodium EDTA 0.1 BHT 0.05 EXAMPLE 4 - THE COSMETIC COMPOSITION OF THE PRESENT INVENTION IN CREAM FORM (Deo Cream NT1123-12-A)
Table 4 below presents a formulation of the cosmetic composition according to the present invention in cream form. Table 4 Component Concentration (wt.-%) Demineralized water 41.7 Aluminum hydrochloride 30.0 Cetosterayl alcohol 7.5 Olus oil 3.8 Ceresin 3.0 Cyclopentasyloxane 2.5 Talc 2.0 Hydroxypropylic starch phosphate 2.0 Steareth-20 1.75 Pantenol 1.5 Perfume 1.1 Dicapryl carbonate 1.0 Dimethiconol, cyclopentasiloxane 1.0 DMDM hydantoin 0.6 2-methyi-S-cydohexylpentanol 0,4 Disodium EDTA 0.1 BHT 0.05 EXAMPLE 5 - THE COSMETIC COMPOSITION OF THE PRESENT INVENTION IN CREAM FORM (called 13-39540-03)
Table 5 below presents a formulation of the cosmetic composition according to the present invention in cream form. WO 2015/172221 11 PCT/BR2015/050058 5 Table 5 Component Concentration (wt.-%) Demineralized water 45.5 Aluminum hydrochloride 30.0 Cetosterayl alcohol 7.5 Ceresin 3.0 Cyclopentasiloxane 2.5 Talc 2.0 Hydroxypropylic starch phostate 2.0 Ceteareth-20 1.75 Pantenol 1.5 Perfume 1.1 Dicapryl carbonate 1.0 Dimethiconol, cyclopeontasiloxane 1.0 DMDM hydantoin 0.6 2,-methyl-5-cyclohexylpoentanol 0.4 Disodium EDTA 0.1 BHT 0.05 EXAMPLE 6 - THE COSMETIC COMPOSTIION PRESENT INVENTION IN CREAM FORM (called 13-39540-04) Table 6 below presents a formulation of the composition according to the present invention in cream form. Table 6 Component Concentration (wt.-%) Demineralized water 44.5 Aluminum hydrochloride 30.0 Cetostearyl alcohol 7.5 Cerasin 3.0 cyclopeontasiloxane 2.5 Talc 2.0 Hydroxypropylic starch phosphate 2.0 Ceteareth-20 1.75 OF THE cosmetic WO 2015/172221 12 PCT/BR2015/050058
Pantenol 1.5 Perfume 1.1 Hydrogenated palm oil 1.0 Dicapryl carbonate 1.0 Dimefhiconol, cyclopentasiloxane 1.0 DMDM hydantoin 0.6 2-methy!-5-cyclohexy!pentanol 0.4 Disodium EDTA 0.1 BHT 0.05
The cosmetic composition of the present invention is prepared in a conventional way, known to those skilled in the art, TESTS:
TEST 1 - INSTRUMENTAL EVALUATION OF THE EFFECT OF 5 THE COMPOSITION OF THE INVENTION (called 13-39540-03) ON ERYTHEMA CAUSED BY THE TAPE-STRIPPING TECHNIQUE. 1.1 -Objective
Evaluating the potential of a calming action of a topical product referring to a composition according to the invention through instrumental 10 measurements of colorimetry. 1.2 Methodology, materials and equipment
Two symmetrical 10cm2 areas having randomized distribution in the front region of the forearms of the patients (a total of 21 participants) were demarcated. One of the areas was used for application of the product 15 and the other was kept as control (untreated area). Colorimetric measurements were made with the equipment Mexameter MX18 - Courge + Khazaka prior to tape-stripping removal (Fita Hipoalergenica TransproeMR) and application of the product (Tb) after 30 tape-stripping removals at each site (TO) and after 30 minutes, 1, 2, 3, 4, 5 and 6 hours from application of 20 the product. 1.3 - Measurement of Erythema - Mexametry
The measurements were carried out by using the equipment Mexameter MX 18, Courage + Khazaka electronic GmbH through a WO 2015/172221 PCT/BR2015/050058 13 measurement probe. The readings were made by applying the probe to the test areas with the pressure permitted by the spring (0.5 N).
The measurement area was 5 mm in diameter. Three measurements were carried out in each area. The measurement consisted in 5 measuring the light absorbed and reflected at the wavelengths for green and red for hemoglobin and wavelengths for green and near infrared for melanin.
The operator positioned the probe vertically, forming a 90-degree angle with the skin and cleaned the probe with the aid of a very soft piece of paper prior to the first reading and between the readings of one area an 10 another, even if it were the control area or the initial measurement of each area.
The reading indicated the degree of erythema of the skin. The scale of the equipment is arbitrary, the reading values indicating greater redness of the skin (erythema). 15 1.4 - Steps of research 1.4.1 -First Step
The participants remained at rest in an air-conditioned room with temperature of 20 ± 2°C and relative humidity of 50 ± 5% for at least 30 minutes prior to each reading; 20 - The participants were told not to smoke; not to come out of the test room without prior authorization of the expert; not to come into contact with the area being tested at any place; not to contact the area being tested in contact with the clothes between the first air-conditioning and the end of the measurements; not to make abrupt movements with any part of the body; 25 and not to allow the test area to get wet;
The participants were evaluated by the dermatologist to confirm the research inclusion criteria;
Two symmetric 10cm2 areas of the region before the forearms having randomized distribution were demarcated. One area was used for 30 application of the product and the other area was kept as negative control (untreated area); and WO 2015/172221 14 PCT/BR2015/050058
One determined the coloration of the areas through arithmetic mean of three measurements (Tb). 1.4.2 - Second Step 30 tape-stripping removals were carried out in the two 5 demarcated areas. The adhesive tapes (TransporeMR) were replaced at each removal; and
One determined the coloration of the demarcated areas through the arithmetic mean of three measurements (TO). 1.4.3 -Third Step 10 - The tested product was applied in a randomized manner, in the amount of Q.G2g in the demarcated region of each participant. The product was spread over the skin with the aid of a latex fingerstall, with light and circular movements until the whole application area was entirely covered and homogeneous. The latex fingerstall was changed in each area; 15 - The measurements were carried out in the following times: • T30min - thirty minutes after application of the product; • T1h - one hour after application of the product; • T2h - two hours after application of the product; • T3h - three hours after application of the product; 20 · T4h - four hours after application of the product; • T5h - five hours after application of the product; • T6h - six hours after application of the product.
The participants were evaluated by the dermatologist at the end of the measurements T6h; and 25 - After the medical evaluation the participants were released. 1.5 - Statistical Analysis
For a statistical analysis of the results, different tests were employed, as follows:
In order to compare the treatments in each time, one used 30 AN OVA, followed by the DUNNET test and to compare the times with regard to the initial time TO, one used the Student test t. WO 2015/172221 15 PCT/BR2015/050058
As said before, the number of participants of the research was 21 and ai! of them completed the study in question.
The trust ievel considered in the comparative analyses was of 5 1.6 -Results 1.6.1 - Measurement of Erythema - Mexametry
Table 7: Measurements, descriptive statistics and results of the comparison
Participant of the 13-3954 0-03 Control 13-39540-03 Control research Tb TO Tb TO A(TO-Tb) A(TO-Tb) 001 242 352 265 358 110 93 002 343 493 363 -1 ‘7 O 4/0 150 115 003 333 454 317 423 121 106 004 251 385 272 399 134 127 005 240 4 Mi"'! 280 451 240 171 006 451 L” L” - I 395 465 100 70 007 361 479 366 459 118 93 008 342 450 354 448 1 DO 94 009 298 456 323 391 i pq -LWU 68 010 357 452 401 467 95 66 Oil 343 430 374 407 87 33 012 276 299 264 323 23 59 013 337 432 368 455 Qt; 87 014 362 452 346 448 QA C/w 102 015 284 377 ηη r -s-sS 1 Λ *’ 4U / 93 ~T"'· ! L· 017 ni n DiZ 477 316 405 165 89 018 234 412 242 376 178 134 019 282 357 306 374 75 68 020 304 458 266 455 154 189 021 267 360 267 336 93 69 022 IPX 365 248 309 80 61 Average 309.7 427.2 317.5 411.1 117.5 93.6 Medium 304.0 450.0 317.0 407.0 108.0 89.0 Minimum 234.0 299.0 242.0 309.0 23.0 33.0 Maximum 451.0 551.0 401.0 478.0 z4Q.Q 189.0 Standard error 11.5 13.1 11.0 11.0 10.0 8.2 IC of 95% [286.6; 332.8] [401.0; 453.3] [295.6; 339.5] [389.1; 433.2] [97.5; 137.4] [77.2; 110.0] Δ(%) with respect to TO 37.9 29.5 % of participants with irritating effect 100.0 100.0 P-Value <0.001*** <0.001.*** *** significant at level 0,1%; **significani at level 1%; ‘significant at level 5% (Student t test)
The TO was higher on average than the Tb for product and control.
Particip ant TO T30- rrsirs T1h T2h T3h T4h T5h T6h Δ(Τ30- min- T0) Δ ¢11 h-T0) Δ (T2h- T0) Δ (T3h- T0) Δ (T4h- T0) Δ {T5h- T0) Δ (T6h- T0) 001 352 217 216 270 265 300 292 275 -135 -136 -82 -87 -52 -60 -77 002 493 308 345 376 409 392 395 402 -185 -148 -117 -84 -101 -98 -91 003 454 225 266 328 337 368 343 346 -229 -188 -126 -117 -86 -111 -108 004 385 224 251 225 251 281 254 248 -161 -134 -160 -134 -104 -131 -137 005 480 326 353 348 361 365 379 378 -154 -127 -132 -119 -115 -101 -102 006 551 437 451 471 458 495 492 484 -114 -100 -80 -93 -56 -59 -67 007 479 370 358 353 369 379 389 381 -109 -121 -126 -110 -100 -90 -98 008 450 313 288 301 322 347 340 351 -137 -162 -149 -128 -103 -110 -99 009 456 332 350 339 389 387 384 380 -124 -106 -117 -67 -69 -72 -76 010 452 359 332 358 338 358 340 361 -93 -120 -94 -114 -94 -112 -91 011 430 320 311 328 309 308 339 351 -110 -119 -102 -121 -122 -91 -79 012 299 263 275 235 280 263 289 276 -36 -24 -64 -19 -36 -10 -23 013 432 373 358 353 380 382 376 360 -59 -74 -79 -52 -50 -56 -72 014 452 344 352 368 358 356 361 364 -108 -100 -84 -94 -96 -91 -88 015 377 278 273 279 300 309 311 323 -99 -104 -98 -77 -68 -66 -54 017 477 320 347 372 377 400 394 376 -157 -130 -105 -100 -77 -83 -101 018 412 240 240 266 257 265 278 264 -172 -172 -146 -155 -147 -134 -148 019 357 244 248 270 270 264 283 290 -113 -109 -87 -87 -93 -74 -67 020 458 393 366 401 398 407 442 401 -65 -92 -57 -60 -51 -16 -57 021 360 254 293 282 305 326 307 337 -106 “87 -78 -55 -34 -53 -23 022 365 305 277 287 292 252 274 280 -60 -88 -78 -73 -113 -91 -85 Average 427.2 306.S 311.9 324.3 334.5 343.0 345.8 344.2 -120.3 -115.3 -102.9 -92.7 -84.1 -81.4 -83.0 Medium 450.Q 313.0 311.0 328.0 337.0 356.0 340.0 351.0 -113.0 -119.0 -98.0 -93.0 -93.0 -90.0 -85,0 Minimum 299,0 217 0 216.0 225.0 251,0 252.0 254,0 248,0 -229,0 -188.0 -160,0 -155,0 -147.0 -134.0 -148.0 Maximum 551.0 437.0 451.0 471.0 458.0 495.0 492.0 484.0 -36.0 -24.0 -57.0 -19.0 -34.0 -10.0 -23.0 Standard 13.1 13.3 12.3 13.0 12.3 13.3 13.1 12.4 10.1 8.1 6.3 7.0 6.6 7.1 6.6 error IC de [401,0; [280.4; [287.4; [298.3 [309.9 [316.4; [319,6; [319.4 [- 1 Ad 5· [- Ή1 4‘ [" 115 5' [-106,7; [-97.3; - [-95.5; [-96,3; - 95% 453,3] 333.4] 336.5] 350.2] 359.2] 369.7] 372.0] 369.0]-100.1 ] -99.2] -90.3] -78.6] 71.0] -67.2] 69.7] Δ(%) with respect to the TO -28.2 -27.0 -24.1 -21.7 -19.7 -19.1 -19.4 WO 2015/172221 16 PCT/BR2015/050058 5 Table 8: Measurements and descriptive statistics of the product_ WO 2015/172221 17 PCT/BR2015/050058
Table 9: Descriptive measurements and statistics of the control Particip ant TO T30- T1h Δ(Τ30 Δ Δ Δ Δ Δ Δ min T2h T3h T4h T5h T6h -min- (T1h- (T2h- (T3h- (T4h- (T5h- (T6h- TO) TO) TO) TO) TO) TO) TO) 'ί- Ο o 358 261 281 290 320 332 335 346 -97 -77 -68 -38 -26 -23 -12 002 478 397 429 399 421 413 422 433 -81 -49 -79 -57 -65 -56 -45 003 423 289 328 319 321 346 331 332 -134 -95 -104 -102 -77 -92 -91 004 399 231 266 261 268 293 277 286 -168 -133 -138 -131 -106 -122 -113 005 451 349 344 349 392 346 366 361 -102 -107 -102 -59 -105 -85 -90 006 465 416 411 391 402 406 399 389 -49 -54 -74 -63 -59 -66 -76 007 459 387 372 351 356 375 384 367 -72 -87 -108 -103 -84 -75 -92 008 448 356 334 344 346 377 359 367 -92 -114 -104 -102 -71 -8S -81 009 391 356 361 343 354 365 361 364 -35 -30 -48 -37 -26 -30 -27 010 467 393 382 385 375 428 394 379 -74 -85 -82 -92 -39 -73 -88 011 407 347 334 331 352 353 364 360 -60 -73 -76 -55 -54 -43 -47 012 323 270 275 235 259 250 260 270 -53 -48 -88 -64 -73 -63 -53 013 455 437 425 405 429 422 403 416 -18 -30 -50 -26 -33 -52 -39 014 448 363 354 380 386 389 375 371 -85 -94 -68 -62 -59 -73 -77 015 407 328 336 323 324 344 331 349 -79 -71 -84 -83 -63 -76 -58 017 405 293 316 332 340 352 338 353 -112 -89 -73 -65 -53 -67 -52 018 376 217 219 240 269 277 282 257 -159 -157 -136 -107 -99 -94 -119 019 374 272 291 276 289 284 304 295 -102 -83 -98 -85 -90 -70 -79 020 455 365 346 326 324 349 347 350 -90 -109 -129 -131 -106 -108 -105 021 336 267 258 275 297 302 302 328 -69 -78 -61 -39 -34 -34 -8 022 309 278 260 247 240 226 203 223 -31 -49 -62 -69 -83 -106 -86 Average 411.1 327.2 329.6 323.9 336.4 344.2 339.9 342.7 -83.9 -81.5 -87.2 -74.8 -66.9 -71.3 -68.5 Medium 407,0 347.0 334.0 331,0 340,0 349.0 347.0 353.0 -81.0 -83.0 -82.0 -65.0 -65,0 -73.0 -77.0 Minimum 309.0 217.0 219.0 235.0 240.0 226.0 203.0 223.0 -168.0 -157.0 -138.0 -131.0 -106.0 -122.0 -119.0 Maximum 478.0 437.0 429.0 405.0 429.0 428.0 422.0 433.0 -18.0 -30.0 -48.0 -26.0 -26.0 -23.0 -8.0 Standard error 11.0 13.7 12.5 11.6 11.7 12.1 11.7 11.2 8.4 7.0 5.7 6.6 5.7 5.7 6.8 IC of [389.1; [299.9; [304,6; [300.7 [313.0 [320; [316.4; [32Q.2; [- 100.7; -67.1] [-95.6; [-98.6; [-87.9; - [-78,3; - [-82.7; [-82.1; - 95% 433.2] 354.6] 354.6] 347,1] 359.7] 368.5] 363.3] 365.1] -67.5] -75.8] 61.7] 55.5] -59.9] 54.8] Δ(%) em relagao ao TO -20.4 -19.8 -21.2 -18.2 -16.3 -17.3 -16.7
Table 10: Average and standard error of each treatment per time, and the 5 difference between the treatments Product Control Product - Control i ime Average E.P. Average E.P. Average E.P. TO 427.19 13.08 411.14 11.02 16.05 7.26 TSOmin 306.90 13.26 327.24 13.69 -20.33 7.17 11 h 311.90 12.28 329.62 12.49 -17,71 8.39 T2h 324.29 12.98 323.90 11.60 0.38 7.82 T3h 334.52 12.32 336.38 11.67 -1.86 8.05 WO 2015/172221 18 PCT/BR2015/050058 T4h 343.05 13.32 344.24 12.13 -1.19 8.48 T5h 345.81 13.10 339.86 11.73 5.95 9.21 T6h 344.19 12.40 342.67 11.24 1.52 8.23
Table 11: Percentage of variation on the average with respect to the time TO, and percentage of participants with positive and negative effect Time Product - Control % of variation with respect to the TO % of participants with positive effect % of participants with negative effect T30min -7.7 85.7 14.3 T1h -7.2 85.7 14.3 T2h -2.9 85.7 14.3 T3h -3.5 85.7 14.3 T4h -3.4 76.2 19.0 T5h -1.7 76.2 23.8 T6h -2.8 71.4 28.6
The product exhibited greater reduction with respect to the TO in 5 the average values of erythema compared with the control in the times T30min (p-value < 0.0001), T1h (p-value = 0.0001), T2h {p-value = 0.0155), T3h (p-value = 0.0253) and T4h (p-value = 0.0163). No significant differences were found between the product and the control in the times T5h (p-value = 0.2834) and T6h (p-vaiue = 0.0528). 10 The times T30min, T1h, T2h, T3h, T4h, T5h and T6h were lower than the time TO for the product (p-values < 0.001).
Wherein: cm2: square centimeters; g: grams; 15 h: hours; no.: number; °C: degrees Centigrade;
Tx: time after x hours of application of the product. 1.7 - Conclusion 20 After the statistical analysis of the results, one can conclude that the composition of the invention promoted reduction of the erythema caused by the tape-stripping technique until the time of 4 hours. WO 2015/172221 PCT/BR2015/050058 19
TEST 2 - INSTRUMENTAL EVALUATION OF THE EFFECT OF THE COMPOSITION OF THE INVENTION (called 13-29540-04) ON THE ERYTHEMA CAUSED BY THE TAPE-STRIPPING TECHNIQUE 2.1 - Objective 5 Evaluating the potential of calming action of a topical product referring to a composition according to the invention through instrumental colorimetric measurement. 2.2 - Methodology, materials and equipment
Two symmetric 10cm2 areas of randomized distribution in the 10 region before the forearms of the participants (a total of 21 participants) were demarcated. One of the areas was used for application of the product and the other was kept as control (untreated area). Colorimetric measurements were made with the equipment Mexameter MX18 - Courage + Khazaka before tape-stripping removal (Fita Hipoalergenica TransporeMR) and 15 application of the product (Tb), after the 30 tape-stripping removals at each site (TO) and after 30 minutes, 1,2, 3, 4, 5 and 6 hours of application of the product. 2.3 - Measurement of Erythema - Mexametry
The measurements were carried out by using the equipment 20 Mexameter MX 18, Courage + Khazaka electronic GmbH through a measurement probe. The readings were made by applying the probe to the test areas with the pressure permitted by the spring (0.5 N).
The measurement area was 5 mm in diameter. Three measurements were carried out in each area. The measurement consisted in 25 measuring the light absorbed and reflected at the wavelengths for green and red for hemoglobin and wavelengths for green and near infrared for melanin.
The operator positioned the probe vertically, forming a 90-degree angle with the skin and cleaned the probe with the aid of a very soft piece of paper prior to the first reading and between the readings of one area an 30 another, even if it were the control area or the initial measurement of each area. WO 2015/172221 PCT/BR2015/050058 20
The reading indicated the degree of erythema of the skin. The scale of the equipment is arbitrary, the reading values indicating greater redness of the skin (erythema). 2,4 - Steps of research 5 2.4.1 - First Step
The participants remained at rest in an air-conditioned room with temperature of 20 ± 2°C and relative humidity of 50 ± 5% for at least 30 minutes prior to each reading;
The participants were told not to smoke; not to come out of the 10 test room without prior authorization of the expert; not to come into contact with the area being tested at any place; not to contact the area being tested in contact with the clothes between the first air-conditioning and the end of the measurements; not to make abrupt movements with any part of the body; and not to allow the test area to get wet; 15 - The participants were evaluated by the dermatologist to confirm the research inclusion criteria;
Two symmetric 10cm2 areas of the region before the forearms having randomized distribution were demarcated. One area was used for application of the product and the other area was kept as negative control 20 (untreated area); and
One determined the coloration of the areas through arithmetic mean of three measurements (Tb). 2.4.2 - Second Step 30 tape-stripping removals were carried out in the two 25 demarcated areas. The adhesive tapes (TransporeMR) were replaced at each removal; and
One determined the coloration of the demarcated areas through the arithmetic mean of three measurements (TO). 2.4.3 -Third Step 30 - The tested product was applied in a randomized manner, in the amount of G,02g in the demarcated region of each participant. The product was spread over the skin with the aid of a latex fingerstall, with light and circular movements until the whole application area was entirely covered and homogeneous. The latex fingerstall was changed in each area;
The measurements were carried out in the following times: • TSOmin - thirty minutes after application of the product; 5 · T1h - one hour after application of the product; • T2h - two hours after application of the product; • T3h - three hours after application of the product; • T4h - four hours after application of the product; • T5h - five hours after application of the product; 10 · T6h - six hours after application of the product.
The participants were evaluated by the dermatologist at the end of the measurements T6h; and
After the medical evaluation the participants were released. 2.5 - Statistical Analysis 15 For a statistical analysis of the results, different tests were employed, as follows:
In order to compare the treatments in each time, one used ANOVA, followed by the DUNNET test and to compare the times with regard to the initial time TO, one used the Student test t. 20 As said before, the number of participants of the research was 21 and all of them completed the study in question.
The trust level considered in the comparative analyses was of 96%. 2.6 - Results 25 2.6.1 - Measurement of Erythema - Mexametry
Table 12: Measurements, descriptive statistics and results of the comparison
Participant of the research 13-39540-04 Control 13-39540-04 Control Tb TO Tb TO AfT0-Tb) AfT0-Tb) 0Q1 279 374 265 358 95 93 002 300 426 363 478 126 115 003 303 428 317 423 125 106 004 264 395 272 399 131 127 005 236 412 280 451 176 171 006 403 505 395 465 102 70 WO 2015/172221 PCT/BR2015/050058 21 007 403 484 386 459 81 93 008 358 442 354 448 84 94 009 309 428 323 391 119 68 010 383 459 401 467 76 66 011 350 417 374 407 67 33 012 313 389 264 323 76 59 013 360 407 368 455 47 87 014 326 388 346 448 62 102 015 302 398 335 407 96 72 017 304 344 316 405 40 89 018 244 423 242 376 179 134 019 279 383 306 374 104 68 020 306 410 266 455 104 189 021 220 371 267 336 151 69 022 270 301 248 309 31 61 Average 310.1 408.8 317.5 411.1 98.7 93.6 Medium 304.0 410.0 317.0 407.0 96.0 89,0 Minimum 220.0 301.0 242.0 309.0 31.0 33.0 Maximum 403.0 505.0 401.0 478.0 179.0 189.0 Standard error 11.2 9.8 11.0 11.0 8.8 8.2 !C Of 95% [287.6; 332.6] [389.2; 428.3] [295.6; 339.5] [389.1; 433.2] [81.0; 116.3] [77.2; 110.0] Δ(%) with respect to the TO 31.8 29.5 % of participants with irritating effect 100.0 180.0 P-Vakse <0.001*** <0.001*** *** significant at Sevei 0.1%; **significant at ievei 1%; ‘significant at ievei 5% (t-Student test).
The TO was hither on the average than the Tb for product and controi Tabie 13: Measurements and descriptive statistics of the product
Particip ant TO T30- min T1h T2h T3h T4h T5h T6h Δ(Τ30- min- T0) Δ (T1h- T0) Δ (T2h- TG] Δ (T3h- T0) Δ fT4h- T0) Δ (T5h- T0) Δ (T6h- T0) 001 374 235 257 280 295 334 331 346 -139 -117 -94 -79 -40 -43 -28 002 426 284 263 323 341 328 347 331 -142 -163 -103 -85 -98 -79 -95 003 428 234 266 276 314 340 328 317 -194 -162 -152 -114 -88 -100 -111 004 395 246 276 267 270 295 293 290 -149 -119 -128 -125 -100 -102 -105 005 412 263 273 307 298 304 285 289 -149 -139 -105 -114 -108 -127 -123 006 505 380 390 408 423 441 424 428 -125 -115 -97 -82 -64 -81 -77 007 484 391 388 380 385 389 398 394 -93 -96 -104 -99 -95 -86 -90 008 442 312 304 275 313 319 321 332 -130 -138 -167 -129 -123 -121 -110 009 428 321 336 331 353 401 344 371 -107 -92 -97 -75 -27 -84 -57 010 459 369 375 388 392 416 417 386 -90 -84 -71 -67 -43 -42 -73 011 417 355 323 335 350 350 386 353 -62 -94 -82 -67 -67 -31 -64 012 389 324 305 295 294 311 290 306 -65 -84 -94 -95 -78 -99 -83 WO 2015/172221 22 PCT/BR2015/050058 WO 2015/172221 23 PCT/BR2015/050058 013 407 362 373 342 390 371 354 378 -45 -34 -63 -17 -36 -53 -29 014 388 292 315 330 319 317 297 306 -96 -73 -58 -69 -71 -91 -82 015 398 300 311 309 314 332 311 313 -98 -87 -89 -84 -66 -87 -85 017 344 257 282 280 307 321 303 311 -87 -62 -64 -37 -23 -41 -33 018 423 260 264 283 284 300 290 290 -163 -159 -140 -139 -123 -133 -133 019 383 254 259 258 275 280 294 275 -129 -124 -125 -108 -103 -89 -108 020 410 345 317 312 359 348 335 349 -65 -93 -98 -51 -62 -75 -61 021 371 226 244 264 270 260 271 284 -145 -127 -107 -101 -111 -100 -87 022 301 251 244 245 251 222 213 227 -50 -57 -56 -50 -79 -88 -74 Average 408.8 298.1 303.1 309.0 323.7 332.3 325.3 327.4 -110.6 -105.7 -99.8 -85.1 -76.4 -83.4 -81.3 Medium 410.0 292.0 304.0 307.0 314.0 328.0 321.0 317.0 -107.0 -96.0 -97.0 -84.0 -78.0 -87.0 -83.0 Minimum 301.0 226.0 244. Q 245.0 251.0 222.0 213.0 227.0 -194.0 -163.0 -167.0 -139.0 -123.0 -133.0 -133.0 Maximum 505.0 391.0 390.0 408.0 423.0 441.0 424.0 428.0 -45.0 -34.0 -56.0 -17.0 -23.0 -31.0 -28,0 Standard error 9.8 11.6 10.3 9.7 10.2 11.3 11.1 10.3 8.8 7.7 8.5 6.8 6.7 6.2 6.4 !C of 95% [389.2; [275.0; [282.5; 428.3] 321.2] 323.6] [289.6 [303.3 328.3] 344.1] [309.8; [303.1; 354.9] 347.6] [306.9 348.0] E- 128.3; -93.0] E- 121.1; -90.2] E- 112.9; -86.8] [-98.7; -71.4] [-89.8; -63.1] [-95.8; -71.1] [-94.1; -68.6] Δ{%) am relagao ao TO -27.1 -25.9 -24.4 -20.8 -18.7 -20.4 -19.9 Table 14: Measurements and descriptive statistics of the controi
Partieip ant TO T30- min T1h T2h T3h T4h T5h T8h Δ]Τ30 -mire- T0) Δ (T1h- T8) Δ {T2h- T0) Δ (T3h- T05 Δ (T4h- TG) Δ (T5h- T0) Δ {T8h- ΤΘ) 001 358 261 281 290 320 332 335 346 -97 -77 -68 -38 -26 -23 -12 002 478 397 429 399 421 413 422 433 -81 -49 -79 -57 -65 -56 -45 003 423 289 328 319 321 346 331 332 -134 -95 -104 -102 -77 -92 -91 004 399 231 266 261 268 293 277 286 -168 -133 -138 -131 -106 -122 -113 005 451 349 344 349 392 346 366 361 -102 -107 -102 -59 -105 -85 -90 006 465 416 411 391 402 406 399 389 -49 -54 -74 -63 -59 -66 -76 007 459 387 372 351 356 375 384 367 -72 -87 -108 -103 -84 -75 -92 008 448 356 334 344 346 377 359 367 -92 -114 -104 -102 -71 -89 -81 009 391 356 361 343 354 365 361 364 -35 -30 -48 -37 -26 -30 -27 010 467 393 382 385 375 428 394 379 -74 -85 -82 -92 -39 -73 -88 011 407 347 334 331 352 353 364 360 -60 -73 -76 -55 -54 -43 -47 012 323 270 275 235 259 250 260 270 -53 -48 -88 -64 -73 -63 -53 013 455 437 425 405 429 422 403 416 -18 -30 -50 -26 -33 -52 -39 014 448 363 354 380 386 389 375 371 -85 -94 -68 -62 -59 -73 -77 015 407 328 336 323 324 344 331 349 -79 -71 -64 -83 -63 -76 -58 017 405 293 316 332 340 352 338 353 -112 -89 -73 -65 -53 -67 -52 018 376 217 219 240 269 277 282 257 -159 -157 -136 -107 -99 -94 -119 019 374 272 291 276 289 284 304 295 -102 -83 -98 -85 -90 -70 -79 020 455 365 346 326 324 349 347 350 -90 -109 -129 -131 -106 -108 -105 021 336 267 258 275 297 302 302 328 -69 -78 -61 -39 -34 -34 -8 022 309 278 260 247 240 226 203 223 -31 -49 -62 -69 -83 -106 -86 Average 411.1 327.2 329.6 323.9 336.4 344.2 339.9 342.7 -83.9 -81.5 -87.2 -74.8 -66.9 -71.3 -68.5 WO 2015/172221 PCT/BR2015/050058 24
Medium 407.0 347.0 334.0 331.0 340.0 349.0 347.0 353.0 -81.0 -83.0 -82.0 -65.0 -65.0 -73.0 -77.0 Minimum 309.0 217.0 219.0 235.0 240,0 226.0 203.0 223,0 -168.0 -157.0 -138.0 -131.0 -106.0 -122.0 -119.0 Maximum 478.0 437.0 429.0 405.0 429.0 428.0 422.0 433.0 -18.0 -30.0 -48.0 -26.0 -26.0 -23.0 -8.0 Standard error 11.0 13.7 12.5 11.6 11.7 12.1 11.7 11.2 8.4 7.0 5.7 6.6 5.7 5.7 6.8 iC of [389.1; [299.9; [304.6; [300.7 [313.0 [320; [316.4; [320.2; [- mn 7* [-95.6; [-98.6: [-87.9: - Γ-78.3; - [-82.7; [-82.1:- 95% 433.2] 354.6] 354.6] 347.1] 359.7] 368.5] 363.3] 365.1] -67.1] -67.5] -75.8] 61.7] 55.5] -59.9] 54.8] Δ(%) wtih respect to the TO -20.4 -19.8 -21.2 -18.2 -16.3 -17.3 -16.7 Table 15: Average and standard error of each treatment per time and the difference between the treatments Product Control Product - Cotrol Average E.P. Average E.P. Average E.P. TO 408.76 9.77 411.14 11.02 -2.38 8.14 TSOmin 298.14 11.55 327.24 13.69 -29.10 8.74 T1h 303.10 10.28 329.62 12.49 -26.52 9.26 T2h 308.95 9.67 323.90 11.60 -14.95 7.92 T3h 323.67 10.21 336.38 11.67 -12,71 7.88 T4h 332.33 11.26 344.24 12.13 -11.90 8.05 T5h 325.33 11.14 339.86 11.73 -14.52 7.56 T6h 327.43 10.29 342.67 11.24 -15.24 8.17 5 Table 16: Percentage of variation on the average with respect to the time TO, and percentage of participants with positive and negative effect
Time Product - Control % of variation with respect to the TO % of subjects with positive effect % of subjects with negative effect TSOmin -6.7 85.7 14.3 T1h -6.0 76.2 23.8 T2h -3.2 66.7 33.3 T3h -2.6 66.7 33.3 T4h -2.4 81.0 19.0 T5h -3.1 71.4 28.6 T6h -3.2 66.7 33.3
The product exhibited greater reduction with respect to the TO in the average values of erythema compared with the control in the times 10 TSOmin (p-value = 0.0004) and T1h (p-value = 0.0031). No significant differences were found between product and control in the times T2h ip-value = 0.0571), T3h (p-value = 0,0571), T3h (p-value = 0.2448), T4h ip-value = 0.2311), T5h (p-value = 0.1731) and T6h (p-value = 0.0925). WO 2015/172221 25 PCT/BR2015/050058
The times T30min, T1h, T2h, T3h, T4h, T5h and T6h were iower that the TO for the product (p-values <0.001); wherein: cm2: square centimeters; 5 g: grams; h: hours; no.: number; °C: degrees Centigrade;
Tx: Time after x hours of application of the product. 10 2.7 - Conclusion
After a statistic analysis of the results, one can conclude that the composition of the invention promoted reduction of the erythema caused by the tape-stripping technique until the time of 1 hour.
TEST 3 - INSTRUMENTAL EVALUATION OF THE EFFECT 15 OF THE COMPOSITION OF THE INVENTION (called 13-39540-01) ON THE ERYTHEMA CAUSED BY THE TAPE-STRIPPING TECHNIQUE 3.1 -Objective
Evaluating the potential of a calming action of a topical product referring to a composition according to the invention through instrumental 20 measurements of colorimetry. 3.2 - Methodology, materials and equipment
Two symmetrical 10cm2 areas having randomized distribution in the front region of the forearms of the patients (a total of 21 participants) were demarcated. One of the areas was used for application of the product 25 and the other was kept as control (untreated area). Colorimetric measurements were made with the equipment Mexameter MX18 -- Couage + Khazaka prior to tape-stripping removal (Fita Hipoalergenica TransproeMR) and application of the product (Tb) after 30 tape-stripping removals at each site (TO) and after 30 minutes, 1, 2, 3, 4, 5 and 6 hours from application of 30 the product. 3.3 ~ Measurement of Erythema -- Mexametry WO 2015/172221 26 PCT/BR2015/050058
The measurements were carried out by using the equipment Mexameter MX 18, Courage + Khazaka electronic GmbH through a measurement probe. The readings were made by applying the probe to the test areas with the pressure permitted by the spring (0.5 N). 5 The measurement area was 5 mm in diameter. Three measurements were carried out in each area. The measurement consisted in measuring the light absorbed and reflected at the wavelengths for green and red for hemoglobin and wavelengths for green and near infrared for melanin.
The operator positioned the probe vertically, forming a 90-degree 10 angle with the skin and cleaned the probe with the aid of a very soft piece of paper prior to the first reading and between the readings of one area an another, even if it were the control area or the initial measurement of each area.
The reading indicated the degree of erythema of the skin. The 15 scale of the equipment is arbitrary, the reading values indicating greater redness of the skin (erythema). 3.4 - Steps of research 3.4.1 - First Step
The participants remained at rest in an air-conditioned room with 20 temperature of 20 ± 2°C and relative humidity of 50 ± 5% for at least 30 minutes prior to each reading;
The participants were told not to smoke; not to come out of the test room without prior authorization of the expert; not to come into contact with the area being tested at any place; not to contact the area being tested 25 in contact with the clothes between the first air-conditioning and the end of the measurements; not to make abrupt movements with any part of the body; and not to allow the test area to get wet;
The participants were evaluated by the dermatologist to confirm the research inclusion criteria; 30 - Two symmetric 10cm2 areas of the region before the forearms having randomized distribution were demarcated. One area was used for WO 2015/172221 27 PCT/BR2015/050058 application of the product and the other area was kept as negative control (untreated area); and
One determined the coloration of the areas through arithmetic mean of three measurements (Tb). 5 3.4.2 - Second Step 30 tape-stripping removals were carried out in the two demarcated areas. The adhesive tapes (TransporeMR) were replaced at each removal; and
One determined the coloration of the demarcated areas through 10 the arithmetic mean of three measurements (TO). 3.4.3 -Third Step
The tested product was applied in a randomized manner, in the amount of 0.02g in the demarcated region of each participant. The product was spread over the skin with the aid of a latex fingerstall, with light and 15 circular movements until the whole application area was entirely covered and homogeneous. The latex fingerstall was changed in each area;
The measurements were carried out in the following times: ® TSOmin - thirty minutes after application of the product; ® T1 h - one hour after application of the product; 20 ® T2h - two hours after application of the product; ® T3h - three hours after application of the product; ® T4h - four hours after application of the product; ® T5h - five hours after application of the product; ® T6h - six hours after application of the procuct. 25 - The participants were evaluated by the dermatologist at the end of the measurements T6h; and
After the medical evaluation the participants were released. 3.5 - Statistical Analysis
For a statistical analysis of the results, different tests were 30 employed, as follows: WO 2015/172221 PCT/BR2015/050058 28
In order to compare the treatments in each time, one used AN OVA, foiiowed by the DUNNET test and to compare the times with regard to the initial time TO, one used the Student test t.
As said before, the number of participants of the research was 21 5 and ail of them completed the study in question.
The trust level considered in the comparative analyses was of 96%. 3.6 - Results 3.6.1 - Measurement of Erythema - Mexametry 10
Table 17: Measurements, descriptive statistics and results of the comparison
Participant da 13-39540-01 Control 13-39540-01 Control pesquisa Tb TO Tb TQ A(TO-Tb) A(TO-Tb) 001 338 428 334 428 90 94 002 252 400 278 401 148 123 003 221 354 207 291 133 84 004 292 391 269 396 99 127 005 326 433 334 389 107 55 006 176 323 178 334 147 156 007 365 479 342 451 114 109 008 303 397 268 393 94 125 009 311 421 339 420 110 81 010 245 398 248 391 153 143 011 209 356 238 350 147 112 012 230 363 247 361 133 114 013 278 383 304 486 105 182 014 340 415 347 436 75 89 015 237 318 225 322 81 97 016 228 352 258 368 124 110 017 270 381 234 339 111 105 018 284 411 311 406 127 95 019 226 318 231 318 92 87 020 288 425 263 372 137 109 021 300 362 292 365 62 73 Average 272,3 386,1 273.7 381.8 113.8 108.1 Medium 278.0 391.0 268.0 389.0 111.0 109.0 Minimum 176.0 318.0 178.0 291.0 62.0 55.0 Maximum 365.0 479.0 347.0 486.0 153.0 182.0 Standard error 10.8 9.1 10.5 10.4 5.7 6.3 !C of 95% [250.8; [367.9; [252.6; [360.9; [102.4; 125.1] [95.5; 120.7] WO 2015/172221 29 PCT/BR2015/050058 293.8] 404.3] 294.8] 402.6] Δ(%) with respect to the TO 41.8 39.5 % of participants with irritating effect 100.0 100.0 P-Value <0.001*** <0.001*** 4 *** significant at level 0.1%; ^significant at level 1%; ^significant at level 5% (t-Student test). 5 The TO was higher on the average than the Tb for product and control 8 Table 18: Measurements and descriptive statistics of the product_
Particip ant TO Τ3Θ- min T1h T2h T3h T4h T5h T6h Δ(Τ30- min- TO} Δ (T1h~ TO) Δ (T2h- T0] Δ (T3h~ TO) Δ (T4h- T0) Δ (T5h- T0) Δ (T6h- T0) 001 428 331 345 371 371 366 376 364 -97 -83 -57 -57 -62 -52 -64 002 400 270 300 320 320 308 304 317 -130 -100 -80 -80 -92 -96 -83 003 354 247 260 232 261 209 219 234 -107 -94 -122 -93 -145 -135 -120 004 391 273 288 313 328 312 321 322 -118 -103 -78 -63 -79 -70 -69 005 433 298 305 303 302 314 336 346 -135 -128 -130 -131 -119 -97 -87 006 323 154 159 167 164 168 172 210 -169 -164 -156 -159 -155 -151 -113 007 479 328 325 300 360 386 376 389 -151 -154 -179 -119 -93 -103 -90 008 397 263 279 292 277 297 309 291 -134 -118 -105 -120 -100 -88 -106 009 421 302 312 326 336 332 351 339 -119 -109 -95 -85 -89 -70 -82 010 398 282 283 304 305 302 298 303 -116 -115 -94 -93 -96 -100 -95 011 356 232 234 241 245 252 276 257 -124 -122 -115 -111 -104 -80 -99 012 363 244 234 227 254 268 242 255 -119 -129 -136 -109 -95 -121 -108 013 383 288 283 303 306 325 319 335 -95 -100 -80 -77 -58 -64 -48 014 415 353 337 363 379 360 384 392 -62 -78 -52 -36 -55 -31 -23 015 318 287 277 291 291 300 307 319 -31 -41 -27 -27 -18 -11 1 016 352 213 202 217 224 254 244 293 -139 -150 -135 -128 -98 -108 -59 017 381 280 318 317 315 319 321 326 -101 -63 -64 -66 -62 -60 -55 018 411 284 270 280 287 324 328 356 -127 -141 -131 -124 -87 -83 -55 019 318 230 226 239 272 255 264 260 -88 -92 -79 -46 -63 -54 -58 020 425 310 300 302 297 291 345 345 -115 -125 -123 -128 -134 -80 -80 021 362 328 317 320 356 353 333 352 -34 -45 -42 -6 -9 -29 -10 Average 386.1 276.0 278.8 287.0 297.6 299.8 306.0 314.5 -110.0 -107.3 -99.0 -88.5 -86.3 -80.1 -71.6 Medium 391.0 282.0 283.0 302.0 302.0 308.0 319.0 322.0 -118.0 -109.0 -95.0 -93.0 -92.0 -80.0 -80.0 Minimum 318.0 154.0 159.0 167.0 164.0 168.0 172.0 210.0 -169.0 -164.0 -179.0 -159.0 -155.0 -151.0 -120.0 Maximum 479.0 353.0 345.0 371.0 379.0 388.0 384.0 392.0 -31.0 -41.0 -27.0 -6.0 -9.0 -11.0 1.0 Standard 9.1 10.Q 10.1 10.9 11.3 11.4 11.8 10.8 7.5 7.3 8.8 8.7 8.S 7.6 7.2 error iC of [367.9; [256; [258.5; [265.3 [275.1 [277; [282.4; [293; [- 1· [-122; [- 11O' [-105.8; [-102.2; [-95.3; [-85.9; - 95% 404.3] 296.1] 299] 308.8] 320.1] 322.5] 329.5] 336.1] ) In- Sr* · ¥ j -95] -92.8] -81.9] -71.1] -70.4] -65] 57.2] Δ(%) with respect to the TO -28.5 -27.8 -25.7 -22.9 -22.4 -20.8 -18.5 Table 19: Measurements and descriptive statistics of the control_ Particip TO T30- T1h T2h T3h T4h T5h T6h Δ(Τ30 Δ Δ Δ Δ Δ Δ WO 2015/172221 PCT/BR2015/050058 30 arst min -min- T0) (T1h- T0| (T2h- T0) (T3h- T0) {T4h- TO) (TSh- T0) |T6h- TG) 001 428 340 351 382 381 384 357 379 -88 -77 -46 -47 -44 -71 -49 002 401 326 329 337 338 323 333 331 -75 -72 -64 -63 -78 -68 -70 003 291 245 243 250 249 246 241 234 -46 -48 -41 -42 -45 -50 -57 004 396 283 315 339 360 352 343 369 -113 -81 -57 -36 -44 -53 -27 005 389 325 324 331 319 333 349 344 -64 -65 -58 -70 -56 -40 -45 006 334 180 229 203 214 248 251 260 -154 -105 -131 -120 -86 -83 -74 007 451 323 360 337 349 382 307 348 -128 -91 -114 -102 -69 -144 -103 008 393 288 296 308 292 294 287 321 -105 -97 -85 -101 -99 -106 -72 009 420 361 343 348 368 365 398 383 -59 -77 -72 -52 -55 -22 -37 010 391 281 306 325 326 325 323 343 -110 -85 -66 -65 -66 -68 -48 011 350 268 267 262 285 293 306 310 -82 -83 -88 -65 -57 -44 -40 012 361 270 292 261 312 282 287 301 -91 -69 -100 -49 -79 -74 -60 013 486 366 377 388 385 399 392 408 -120 -109 -98 -101 -87 -94 -78 014 436 396 397 412 421 416 432 419 -40 -39 -24 -15 -20 -4 -17 015 322 270 277 262 267 275 296 294 -52 -45 -60 -55 -47 -26 -28 016 368 244 222 241 248 264 262 301 -124 -146 -127 -120 -104 -106 -67 017 339 288 293 310 303 301 305 296 “51 -46 -29 -36 -38 -34 -43 018 406 319 313 318 312 344 316 338 -87 -93 -88 -94 -62 -90 -68 019 318 245 225 256 260 260 270 276 -73 -93 -62 -58 -58 -48 -42 020 372 293 290 279 331 316 348 357 -79 -82 -93 -41 -56 -24 -15 021 365 305 296 278 308 313 329 316 -60 -69 -87 -57 -52 -36 -49 Average 381,8 296.0 302.1 306,0 315,6 319.8 320,6 329,9 -85.8 -79,6 -75.7 -66.1 -62,0 -61.2 -51.9 Medium 389.0 288.0 296.0 310.0 312,0 316.0 316.0 331.0 -82.0 -81.0 -72.0 -58.0 -57.0 -53.0 -49.0 Minimum 291.0 180.0 222.0 203,0 214.0 246.0 241.0 234.0 -154.0 -146.0 -131.0 -120.0 -104.0 -144.0 -103.0 Maximum 486,0 396.0 397.0 412,0 421,0 416.0 432,0 419,0 -40.0 -39,0 -24.0 -15.0 -20,0 -4.0 -15.0 Standard error 10.4 10.7 10.6 11.7 11.3 10.9 10.7 10.2 6.7 5.4 6.4 6.4 4.6 7.5 4.8 !C of [360.9; [274.6; [281; [282.6 [293.1 [298; [299.2; [309.4; [-99.2; [-90.4; [-88.6; [-78.9; - [-71.1; - [-76.2; [-61.4; - 95% 402,6] 317.4] 323.3] 329.5] 338.21 341.6] 341.9] 350.4] -72.3] -68.8] -62.9] 53.4] 52.9] -46,2] 42.4] A(%) with respect to the TO -22.5 -20.9 -19.8 -17.3 -16.2 -16.0 -13.8
Table 20: Average and standard error of each treatment per time, and of the difference between the treatments_
Product Control Product - Control
Time
Average E.P. Average E.P. Average E.P. TO 386.10 9.10 381.76 10.42 4.33 7.32 TSOmin 276.05 10.01 296.00 10.71 -19.95 5.77 T1h 278.76 10.14 302.14 10.58 -23.38 6.72 T2h 287.05 10.88 306.05 11.70 -19.00 6.01 T3h 297.62 11.25 315.62 11.28 -18.00 6.53 T4h 299.76 11.38 319.76 10.90 -20.00 6.49 T5h 305.95 11.79 320.57 10.67 -14.62 7.50 T6h 314.52 10.76 329.90 10.24 -15.38 7.05
Table 21: Porcentage of variation in the average with respect to the time TO, and percentage of participants with positive and negative effect
Time Produto - Controie % of variation with respect to the TO % of participants with positive effect % of participants with negative effect T30min -6.0 85.7 14.3 T1h -6.9 81.0 19.0 T2h -5.8 85.7 14.3 T3h -5.6 81.0 19.0 T4h -6.1 81.0 19.0 T5h -4.7 66.7 33.3 T6h -5.0 71.4 28.6 WO 2015/172221 31 PCT/BR2015/050058
The product exhibited greater reduction with respect to the TO in 5 the average values of erythema compared with the control in the times T30min (p-value = 0.0010). T1h (p-value = 0.0001), T2h (p-value = 0.0008), T3h (p-value = 0.0050), T4b (p-value = 0.0020), T5h (p-value = 0.0136) and T6h (p-value = 0.0031).
The times T30min, T1h, T3h, T4h, T5h and T6h were lower 10 than the time TO for the product (p-values <0.001).
Wherein:
Cm2: square centimeters; G: grams; H: hours; 15 No.: number; °C: Degrees Celsius;
Tx: Time after x hours of application of the product. 6,4 - Conclusion
After a statistic analysis of the results, one can conclude that the 20 composition of the invention promoted reduction of the erythema caused by the tape-stripping technique until the time of 6 hours. TEST 4 - INSTRUMENTAL EVALUATION OF THE EFFECT OF THE COMPOSITION OF THE INVENTION (called 13-39540-02) ON THE ERYTHEMA CAUSED BY THE TAPE-STRIPPING TECHNIQUE 25 4.1 - Objective
Table 22: Measurements, descriptive statistics and results of the comparison
Participant of the research 13-39540-02 Control 13-39540-02 Control Tb TO Tb TO A(TO-Tb) A(TO-Tb) 001 318 425 334 428 107 94 002 278 391 278 401 113 123 003 211 290 207 291 79 84 004 308 436 269 396 128 127 005 348 455 334 389 107 55 006 168 326 178 334 158 156 007 326 473 342 451 147 109 008 304 379 268 393 75 125 009 317 407 339 420 90 81 010 253 383 248 391 130 143 011 279 364 238 350 85 112 012 265 379 247 361 114 114 013 318 435 304 486 117 182 014 325 418 347 436 93 89 015 233 319 225 322 86 97 016 236 349 258 368 113 110 017 232 314 234 339 82 105 018 336 447 311 406 111 95 019 227 303 231 318 76 87 020 291 395 263 372 104 109 021 318 399 292 365 81 73 Average 280.5 385.1 273.7 381.8 104.6 108.1 Medium 291.0 391.0 268.0 389.0 107.0 109.0 Minimum 168.0 290.0 178.0 291.0 75.0 55.0 Maximum 348.0 473.0 347.0 486.0 158.0 182.0 Standard error 10.5 11.5 10.5 10.4 5.1 6.3 IC Of 95% [259.5: 301.6] [362.1: 408.1] [252.6: 294.8] [360.9: 402.6] [94.4; 114.7] [95.5; 120.7] Δ(%) with respect to the TO 37.3 39.5 % of participants with irritaging effect 100.0 100.0 P-Value <0.001*** <0.001*** *** significant at level 0.1%; “significant at level 1%; ‘significant at level 5% WO 2015/172221 32 PCT/BR2015/050058 (t-Student test).
The TO was higher on the average than the Tb for product and control
Table 23: Measurements and descriptive statistics of the product
ParticiD T30-........................................................................................Δ(Τ3°- Δ........Δ....... Δ .........Δ..... Δ ......Δ..... ant Τ0 m η T1h T2h T3h T4h TSh T6h miil" (T1h- {T2h- (T3h- {T4h- (TSh- (T6h- TO) TO) TO) TO) TO) TO) TO) WO 2015/172221 PCT/BR2015/050058 33 001 425 326 358 363 396 373 372 359 -99 -67 -62 -29 -52 -53 -66 002 391 246 262 292 290 292 286 294 -145 -129 -99 -101 -99 -105 -97 003 290 216 193 196 213 195 192 202 -74 -97 -94 -77 -95 -98 -88 004 436 313 345 386 384 378 360 396 -123 -91 -50 -52 -58 -76 -40 005 455 290 301 297 303 310 336 364 -165 -154 -158 -152 -145 -119 -91 006 326 162 180 180 172 228 217 215 -164 -146 -146 -154 -98 -109 -111 007 473 315 337 312 325 355 327 360 -158 -136 -161 -148 -118 -146 -113 008 379 280 288 294 292 299 298 307 -99 -91 -85 -87 -80 -81 -72 009 407 312 324 319 326 328 337 326 -95 -83 -88 -81 -79 -70 -81 010 383 274 296 304 319 324 322 301 -109 -87 -79 -64 -59 -61 -82 011 364 284 271 271 281 279 289 289 -80 -93 -93 -83 -85 -75 -75 012 379 228 228 260 248 269 266 273 -151 -151 -119 -131 -110 -113 -106 013 435 391 390 405 408 415 415 421 -44 -45 -30 -27 -20 -20 -14 014 418 370 354 372 400 383 380 399 -48 -64 -46 -18 -35 -38 -19 015 319 293 281 274 290 275 281 297 -26 -38 -45 -29 -44 -38 -22 016 349 201 189 219 229 247 248 282 -148 -160 -130 -120 -102 -101 -67 017 314 248 238 269 272 264 270 269 -66 -76 -45 -42 -50 -44 -45 018 447 333 317 338 325 339 336 389 -114 -130 -109 -122 -108 -111 -58 019 303 216 209 224 243 241 253 259 -87 -94 -79 -60 -62 -50 -44 020 395 313 290 299 338 304 317 336 -82 -105 -96 -57 -91 -78 -59 021 399 355 347 339 386 379 353 381 -44 -52 -60 -13 -20 -46 -18 Averate 385,1 284.1 285.6 295,9 306,7 308.4 307,4 320,0 -101,0 -99.5 -89.2 -78.4 -76,7 -77.7 -65.1 Medium 391.Q 290.0 290.0 297.0 303.0 304.0 317.0 307.0 -99.0 -93.0 -88.0 -77.0 -80.0 -76.0 -67,0 Minimum 290.0 162.0 180.0 180.0 172.0 195.0 192.0 202.0 -165.0 -160.0 -161.0 -154.0 -145.0 -146.0 -113.0 Maximum 473.0 391.0 390.0 405.0 408.0 415.0 415.0 421.0 -26.0 -38.0 -30.0 -13.0 -20.0 -20.0 -14.0 Standard error 11.5 12.8 13.4 13.1 14.2 12.7 12.1 13.2 9.3 8.0 8.3 9.9 7.3 7,2 6.8 !C of 95% [362.1; 408,1] [258.5; [258.9; 309.7] 312.3] [269.6 322.1] [278.3 [282.9; [283.1; ; 335] 333.9] 331.6] [293.5 346.4] E- 119.7; -82.3] [ 115.6; -83.4] E- 105.8; -72.7] [-98.3; -58.6] [-91.2; -62.2] [-92.1; -63,3] [-78.7; -51.6] Δ(%) with respect to the TO -26.2 -25.8 -23,2 -20.4 -19.9 -20,2 -16.9
Table 24: Measurements and descriptive statistics of the control Particip a rit TO Τ3Θ- min T1h T2h T3h T4h TSh TSh Δ(Τ3Θ TO) Δ (T1h- T0) Δ (T2h- T0) Δ (T3h~ TO) Δ (T4h- T0) Δ (T5h- T0) Δ (TSh- T0) 001 428 340 351 382 381 384 357 379 -88 -77 -46 -47 -44 -71 -49 002 401 326 329 337 338 323 333 331 -75 -72 -64 -63 -78 -68 -70 003 291 245 243 250 249 246 241 234 -46 -48 -41 -42 -45 -50 -57 004 396 283 315 339 360 352 343 369 -113 -81 -57 -36 -44 -53 -27 005 389 325 324 331 319 333 349 344 -64 -65 -58 -70 -56 -40 -45 006 334 180 229 203 214 248 251 260 -154 -105 -131 -120 -86 -83 -74 007 451 323 360 337 349 382 307 348 -128 -91 -114 -102 -69 -144 -103 008 393 288 296 308 292 294 287 321 -105 -97 -85 -101 -99 -106 -72 009 420 361 343 348 368 365 398 383 -59 -77 -72 -52 -55 -22 -37 WO 2015/172221 PCT/BR2015/050058 34 010 391 281 306 325 326 325 323 343 O -85 -66 -65 -66 -68 -48 011 350 268 267 262 285 293 306 310 -82 -83 -88 -65 -57 -44 -40 012 361 270 292 261 312 282 287 301 -91 -69 -100 -49 -79 -74 -60 013 486 366 377 388 385 399 392 408 -120 -109 -98 -101 -87 -94 -78 014 436 396 397 412 421 416 432 419 -40 -39 -24 -15 -20 -4 -17 015 322 270 277 262 267 275 296 294 -52 -45 -60 -55 -47 -26 -28 016 368 244 222 241 248 264 262 301 -124 -146 -127 -120 -104 -106 -67 017 339 288 293 310 303 301 305 296 -51 -46 -29 -36 -38 -34 -43 018 406 319 313 318 312 344 316 338 -87 -93 -88 -94 -62 -90 -68 019 318 245 225 256 260 260 270 276 -73 -93 -62 -58 -58 -48 -42 020 372 293 290 279 331 316 348 357 -79 -82 -93 -41 -56 -24 -15 021 365 305 296 278 308 313 329 316 -60 -69 -87 -57 -52 -36 -49 Average 381,8 296.0 302.1 306.0 315.6 319.8 320,6 329,9 -85.8 -79.6 -75.7 -66.1 -62.0 -61.2 -51.9 Medium 389.0 288.0 296.0 310.Q 312.0 316.0 316.0 331.0 -82.0 -81.0 -72.0 -58.0 -57.0 -53.0 -49.0 Minimum 291.0 180.0 222.0 203.0 214.0 246.0 241,0 234.0 -154.0 -146.0 -131.0 -120.0 -104.0 -144.0 -103.0 Maximum 486.0 396.0 397.0 412.0 421.0 416.0 432,0 419.0 -40.0 -39.0 -24.0 -15.0 -20.0 -4.0 -15.0 Standard error 10.4 10.7 10.6 11.7 11.3 10.S 10.7 10.2 6.7 5.4 6.4 6.4 4.6 7.5 4.6 IC of 95% [360.9; 402,6] [274.6; [281; 317.4] 323.3] [282.6 [293,1 329.51338.2i [298; [299.2; [309.4; 341.6] 341.9] 350.4} [-99.2; -72.3) [-90.4; -68.8] [-88.6; -62.9] [-78.9; -53.4] [-71.1; - 52.9] [-76.2; -46.2] [-61.4;-42.4 j Δ(%) with respect to the TO -22.5 -20.9 -19.6 -17.3 -16.2 -16.0 -13.6
Table 25: Average and standard error of each treatment per time, and of the Producut Control Product - Control Time - Average E.P. Average E.P. Average E.P. TO 385.10 11.50 381.76 10.42 3.33 5.94 TSOmin 284.10 12.78 296.00 10,71 -11,90 7.02 T1h 285.62 13.35 302.14 10.58 -16.52 6.78 T2h 295.86 13.13 306.05 11.70 -10.19 6.72 T3h 306.67 14.18 315.62 11,28 -8.95 7.01 T4h 308.43 12.74 319.76 10.90 -11.33 5.56 T5h 307.38 12.12 320.57 10.67 -13.19 5.95 T6h 319.95 13.24 329.90 10.24 -9.95 6.84 difference between the treatments 5 Table 26: Porcentage of variation in the average with respect to the time TO, and percentage of participants with positive and negative effect_
Product - Control
Time % of variation with % of participants with % of participants with respect to the TO positive effect negative effect TSOmin -3.8 71.4 28.6 T1h -5.0 76.2 23.8 T2h -3.3 76.2 19.0 T3h -3.0 66.7 28.6 T4h -3.7 71.4 28.6 WO 2015/172221 35 PCT/BR2015/050058 T5h -4.2 76.2 23.8 T6h -3.3 71.4 19.0
The product exhibited greater reduction with respect to the TO in the average values of erythema compared with the control in the times T30min (p-vaiue = 0.0416), T1h (p-va!ue = 0.0040), and T5h (p-value = 0.332). No significant 5 differences were found between product and control in the times T2h (p-value = 0.0579), T3h (p-vaiue = 0.1489). T4h (p-value 0.0712), and T6h (p-value = 0.0508).
The times T30, T1h, T2h, T3h, T4h, T5h and T6h were lower than the time TO for the product (p-vaiues<0.001). 10 Wherein:
Cm2: square centigrade: G: grams; H: hours;
No.: number; 15 °C = degrees Celsius;
Tx: Time after x hours of application of the product. 6.5 - Conclusion
After a statistical analysis of the results, one can conclude that the composition of the invention promoted reduction of the erythema caused by 20 the tape-stripping technique until the time of 1 hour and in the time of 5 hours. TEST 5 - EVALUATION OF THE REDUCTION OF ERYTHEMA CAUSED BY THE TAPE-STRIPPING TECHNIQUE BY USING THE COMPOSITION OF THE INVENTION (called NT1123-12-A). 25 5.1 Objective
Evaluating the efficacy of the topical product (called BDP 1160.18704.6) referring to a composition according to the in reducing skin erythema induced by mechanical insult and evaluated as a function of the redness of the skin. Ion this study, one evaluated the efficacy of a 30 composition according to the invention (NT1123-12-A) in reducing cutaneous WO 2015/172221 36 PCT/BR2015/050058 erythema with respect to a control (site without application of any products). The evaluations were carried in the following times: tO: right after formation of the erythema induced by the tapestripping method; 5 t0.5: 30 minutes after induction of the erythema and application or non-application of the product; t1: 1 hour after induction of the erythema and application or nonapplication of the product; t2: 2 hours after induction of the erythema and application or 10 non-application of the product; t3: 3 hours after induction of the erythema and application or non-application of the product; t4: 4 hours after induction of the erythema and application or non-application of the product; 15 t5: 5 hours after induction of the erythema and application or non-application of the product. 5.2 - Methodology, materials and equipment
On each voluntary woman (a total of 25 participants), two2.5 x 4.0 cm rectangles were marked with a surgical pen, called sites, on the left or 20 right forearm. After 30 minutes of air-conditioning, the environment controlled at 20 ± °C and 50 ± 5% of relative humidity of the air, 30 tape-stripping removals with Transpore® 3M tape were carried out at each site, followed by the measurements fo erythema by the mexametry and colorimetry technique. These measurements were called basal measurements (tO). After the 25 mechanical insult, the product was applied, and the voluntary women remained at the laboratory for the measurements after 0.5 (30 minutes), 1, 2, 3, 4, 5 and 6 hours. During the whole experiment the climatic conditions were kept constant according to the ranges cited before. At the site intended for the product, 80 pL of the sample under study was applied, one of the sites 30 being used as control (without application of any products). 5.3 - Acquisition of measurements
The measurements were made by using a Mexameter® MX 18 probe, coupled to the equipment Multi Probe Adapter MPA-5 (CKeletronics, Germany). Concomitantly with the measurements, one used an automatized spreadsheet of the software Microsoft® Office Excel 2010 for calculation of 5 the Variation Coefficient (VC/CV) of the readings obtained. One carried out 5 measurements per site in each time. If in 5 measurements the VC/CV presented a value lower than 4%, one would finish the measurements at the site and continue them in the next one; otherwise, the process was restarted by using the colorimeter Byk-Gardner Spectro-Guide Sphere Gloss. For this 10 evaluation, one recorded only the values of a*, which is the axis that ranges from green (-120) to read (+120). The values were recorded on an automatized spreadsheet of the software Microsoft® Office Excel 2010 for calculation of the Coefficient of Variation (CV/VC) of the readings obtained. One carried out 3 measurements per site in each time. If in 3 measurements 15 the CV/VC presented a value lower than 4%, one would finish the measurements at the site and continue the measurements at the next one; otherwise the process was restarted until a CV/VC lower than 4% would be obtained. 5.4 - Results 20 25 30 WO 2015/172221 37 PCT/BR2015/050058 5.4.1 - Evaluation of the reduction of the erythema by mexametry
In evaluating of the reduction of the erythema by mexametry, one measured the erythema values (E) for each voluntary woman, at the site intended for the product and at the control site. Figure 13 shows the average values of Erythema (E) obtained for the product site and control site.
In order to evaluate the homogeneity of t erythema caused by the mechanical insult, the values of erythema measured at each site in the basal time (tO) were statistically compared with each other by using the t-Student test, in pairs, with trust interval of 95%. The result is summarized in Table 27. Table 27 - Comparison of the values of erythema induced after mechanical insult - Value of P. £aproduct vs. Et0 control 0.5533 (non-significant) WO 2015/172221 38 PCT/BR2015/050058
According to the results obtained, there was no statistically significant difference between the sites (P > 0.05), indicating the homogeneity in the values of erythema after the mechanical insult. This indicated that the study was conducted with homogeneous basal values of 5 erythema at the evaluation sites.
In order to evaluate whether there were significant variations in the erythema along the study, the erythema measurements obtained after 0,5; 1;; 2; 3; 4; 5 and 6 hours from application of the product, or the basal measurements (tO) were not compared, carried out right after the mechanical 10 insult (prior to application of the product), by using the single-factor variance analysis method, with Dunnett post-test multiple comparison, considering a = 0.05. The results of the statistical analysis are summarized in Table 28.
Table 28
Summarized data of the statistical analysis. Comparison of the values of erythema formed after the mechanical insult fiOJ vs ti (wherein i - (35, 1, 2, \ 4, 5 and 6 hours from I application). Pvalues
Comparison group Control NT1123-12-A Eto vs. Em P < 0,05 (significant) P < 0,05 (Significant) Eto vs. Eti P < 0,05 (significant) P < 0,05 (Significant) E*o vs. Ea P < 0,05 (significant) P < 0,05 (significant) Eto VS. Ets P < 0,05 (significant) P < 0,05 (significant) Eto vs. Et4 P < 0,05 (significant) P < 0,05 (significant) Eto vs. Ets P < 0,05 (significant) P < 0,05 (significant) Eto vs. Ets P < 0,05 (significant) P < 0,05 (significant)
According to the results, it was possible to find out that there 15 was a statistically significant reduction (P < 0.05) of the skin erythema after 0.5, 1, 2,3, 4, 5 and h hours from application of the composition according to the invention as compared with the initial erythema (tO) and still that at the control site (without application of any products) was also obtained one observed a significant reduction (P < 0.05) in the erythema formed by the 20 mechanical insult after 0.5, 1, 2,3, 4, 5 and 6 hours.
Although one has observed a reduction of the erythema at both sites along the study, it is possible to observe, in Figure 14, which shows the percentage of Reduction of the Erythema (%RE) obtained in each evaluation WO 2015/172221 39 PCT/BR2015/050058 time, what there was a more marked reduction of the erythema at the site intended for the product.
In order to evaluate the significance of the reduction of the erythema along the time, that is, the Calming Effect (EC/CE) provided by the 5 product with respect to the control, one calculated the ratio between the erythema measurements after 0.5, 1, 2,3, 4, 5 and 6 hours with respect to the value obtained right after the mechanical insult (tO), by using Eguation 1. ^ EC^Jt/Ev...................................................................................
Equation 1. Calculation of the Calming Effect (EQ. measurement of the i coloration or the erythema in the time /(/::: 0,5,1,2,3/4,5 and 6h) and E^ -- measurement Ldi/li.hb.®..¢9!^ ϋο n of ihe basaI ev/thema tng ht after tjon),
The values of the Calming Effect obtained for the site with application of the product, in each time, were statistically compared with the 10 values obtained for the control by using the t-Student test, bimodai, in pairs, with trust interval of 95%. The results of the statistical analysis are listed in Attachment VII and are summarized in Table 29.
Table 29_ _ 111111111111111111111111¾^^
Comparison .......group. t0,5 tl t2 \ t.3 t4 t5 t6 NTim-12-A VS. EC Control 0,0014 (significa nt) 0,0281 (significa nt) 0,0563 j 0,0787 (Non- i (Non-significa ; significa nt) i nt) 0,0528 ί 0,1682 j 0,6979 (Non- i (Non- i (Non-significa i significa ; signinca nt) nt) nt)
The reduction of the skin erythema provided by the composition of the 15 invention presented a statistically significant difference (P < 0.05) after 30 minutes and 1 hour from application as compared with the respective control (site without application of any products). This indicated that the product was effective in reducing skin erythema by mechanical insult and evaluated as a function of the redness of the skin until 1 hour after application. 20 5.4.2 -- Evaluation of the reduction of the erythema by colorimetry
In evaluating the reduction of the erythema by colorimetry, one measured the values of the coordinate *a for each volunteer at the site intended for the WO 2015/172221 40 PCT/BR2015/050058 product and at the control site. Figure 15 shows the average value of the Erythema Intensity (+a*).
In order to evaluate the homogeneity of the erythema formed by the mechanical insult, the values of a* measured at each site in the basal 5 time (tO) were statistically compared by using the t-Student test, in pairs, with trust interval of 95%. The results achieved are summarized in table 30.
Table 30
Comparison of the values of the erythema occurrences induced after mechanical insult. Value of P a*tO product vs. a* tO control 0.6682 (non-significant)
According to the results obtained, there was no statistically significant difference between the sites (P>0.05), indicating that there was 10 homogeneity in the values of a* after the mechanical insult. This indicated that the study was conducted with homogeneous basal erythema values for the sites under evaluation.
In order to evaluate whether there were significant alterations in the erythema along the study, the erythema measurements obtained after 15 0.5, 1, 2, 3, 4, 5, and 6 hours from application of the product or non application were compared with the basal measurements (tO) carried out right after the mechanical insult (prior to application of the product), by using the single-factor variance analysis, with post-test of Dunnett multiple comparison, considering a = 0.0.05.The results of the statistical analysis are summarized 20 in Table 31.
Table 31 the mechanical insult itO) vs.ti(wherein i - 0.5,1, 2,3,4,5 e 6h from application). Values of Comparison group Control NT1123-12-A a*to vs. a*to,5 P < 0.05 (significant) P < 0.05 (significant) a*to vs. a*n P < 0.05 (significant) P < 0.05 (significant) a*tovsa*t2 P < 0.05 (significant) P < 0.05 (significant) a*to vs. a*3 P < 0.05 (significant) P < 0.05 (significant) a*to vs. 3**4 P < 0.05 (significant) P < 0.05 (significant) a*to vs. a*f5 P < 0.05 (significant) P < 0.05 (significant) a*to vs. a*t6 P < 0.05 (significant) P < 0.05 (significant) WO 2015/172221 41 PCT/BR2015/050058
According to the results, it was possible to observe that that was a statistically significant reduction (P < 0.05) of the skin erythema after 0.5, 1, 2, 3, 4, 5, and 6 hours from application of the composition according to the invention as compared with the initial erythema (tO), and that in the 5 control site (without application of any products) there was a significant reduction (P < 0.05) in the erythema formed by the mechanical insult after 0.5, 1, 2, 3, 45, and 6 hours. Although there has been a reduction of the erythema at both sites along the study, it is possible to observe, in Figure 16, which shows the percentage of Reduction of Erythema Intensity (%R!E) 10 obtained in each evaluation time, that there was a greater reduction of the erythema at the site intended for the product.
In order to evaluate the Calming Effect (CE/EC), one calculated the ratio between the measurements of a* after 0.5, 1, 2,3, 4, 5, and 6 hours with respect to the value obtained along the mechanical insult (tO), by using 15 Equation 2. I EC = a*t/a*to
Equation 2 - Calculation of the Calming Effect {EC). a*s= measurement of the I coloration of the erythema η the time /(/= 0,5,1,2,3,4,5 e 6h) e = measurement of I the coloration of the basal erythema (right after formation)
The values of the Calming Effect achieved for the site with application of the product, in each time, were statistically compared with the values achieved for the control by using the t-Student test, bimodal, in pairs, with trust interval of 95%. The results of the statistical analysis are 20 summarized in table 32.
Table 32. A comparison of the results in terms of EC between the product and the respective control. Values of P.
Compariso n group (0,5 tl (2 (3 t4 /5 t6 EC κτη?3-ι?- A vs EC Controls 0.,0358 (significant " ) 0,0280 (significant ) 0,5951 (non- sitnifican t) 0/1005 (non significant) 0,5370 (nonsign ifica nt) 0,7799 (nonsign ifica nt) 0,6547 (non- significa nt)
The reduction of the skin erythema provided by the composition according to the invention shows a statistically significant difference (P < 0.05) after 30 minutes and 1 hour from application as compared with the WO 2015/172221 42 PCT/BR2015/050058 respective control (site without application of any products). This indicated that the product was effective in reducing the skin erythema induced by mechanical insult and evaluated as a function of the skin redness until 1 hour from application.
5 TEST 6 - INSTRUMENTAL TEST OF THE EFFECT OF THE COMPOSITION OF THE INVENTION (called 12-33171--07) ON THE ERYTHEMA CAUSED BY THE TAPE-STRIPPING TECHNIQUE 6.1 - Objective
Evaluating the potential of calming action of a topical product 10 referring to a composition according to the invention through instrumental measurements of colorimetry. 6.2 - Methodology, materials and equipment
Two symmetrical 10cm2 areas having randomized distribution in the front region of the forearms of the patients (a total of 19 participants) 15 were demarcated. One of the areas was used for application of the product and the other was kept as control (untreated area). Colorimetric measurements were made with the equipment Mexameter MX18 - Courage + Khazaka prior to tape-stripping removal (Fita Hipoaiergenica TransproeMR) and application of the product (Tb) after 30 tape-stripping 20 removals at each site (TO) and after 30 minutes, 1, 2, 3, 4, 5 and 6 hours from application of the product. 6.3 - Measurement of Erythema - Mexametry
The measurements were carried out by using the equipment Mexameter MX 18, Courage + Khazaka electronic GmbH through a 25 measurement probe. The readings were made by applying the probe to the test areas with the pressure permitted by the spring (0.5 N),
The measurement area was 5 mm in diameter. Three measurements were carried out in each area. The measurement consisted in measuring the light absorbed and reflected at the wavelengths for green and 30 red for hemoglobin and wavelengths for green and near infrared for melanin.
The operator positioned the probe vertically, forming a 90-degree angle with the skin and cleaned the probe with the aid of a very soft piece of WO 2015/172221 43 PCT/BR2015/050058 paper prior to the first reading and between the readings of one area an another, even if it were the control area or the initial measurement of each area.
The reading indicated the degree of erythema of the skin. The 5 scale of the equipment is arbitrary, the reading values indicating greater redness of the skin (erythema). 6.4 - Steps of research 6.4.1 - First Step
The participants remained at rest in an air-conditioned room with 10 temperature of 20 ± 2°C and relative humidity of 50 ± 5% for at least 30 minutes prior to each reading;
The participants were told not to smoke; not to come out of the test room without prior authorization of the expert; not to come into contact with the area being tested at any place; not to contact the area being tested 15 in contact with the clothes between the first air-conditioning and the end of the measurements; not to make abrupt movements with any part of the body; and not to allow the test area to get wet;
The participants were evaluated by the dermatologist to confirm the research inclusion criteria; 20 - Two symmetric 10cm2 areas of the region before the forearms having randomized distribution were demarcated. One area was used for application of the product and the other area was kept as negative control (untreated area); and
One determined the coloration of the areas through arithmetic 25 mean of three measurements (Tb). 6.4.2 - Second Step 30 tape-stripping removals were carried out in the two demarcated areas. The adhesive tapes (TransporeMR) were replaced at each removal; and 30 - One determined the coloration of the demarcated areas through the arithmetic mean of three measurements (TO). 6.4.3 - Third Step WO 2015/172221 44 PCT/BR2015/050058
The tested product was applied in a randomized manner, in the amount of G.02g in the demarcated region of each participant. The product was spread over the skin with the aid of a latex fingerstall, with light and circular movements until the whole application area was entirely covered and 5 homogeneous. The latex fingerstall was changed in each area;
The measurements were carried out in the following times: * T30min - thirty minutes after application of the product; * T1h - one hour after application of the product; ® T2h - two hours after application of the product; 10 ® T3h - three hours after application of the product; « T4h - four hours after application of the product; « T5h - five hours after application of the product; * T6h - six hours after application of the product.
The participants were evaluated by the dermatologist at the end 15 of the measurements T6h; and
After the medical evaluation the participants were released. 6.5 - Statistical Analysis
The software used in the analyses was MINITAB 14 AND XLSTAT 2012. 20 As said before, the number of participants in the research was 19
The trust level considered in the comparative analysis was of 95%. 6.6 - Results 6.6.1 - Erythema measurement - Mexametry 25
Table 33: Measurements, descriptive statistics and results of the comparison
Subject 12-33171-07 Control 12-33171-07 Control Tb TO Tb TO A(TO-Tb) A(TQ-Tb) 002 222 325 224 291 103 67 004 262 293 264 322 31 58 005 173 291 198 256 118 58 006 255 346 267 323 91 56 007 147 346 174 213 199 39 008 238 369 246 338 131 92 009 209 258 209 334 49 125 010 157 266 192 172 109 -20 WO 2015/172221 45 PCT/BR2015/050058 012 187 269 162 285 82 123 013 328 383 340 364 55 24 014 163 264 117 258 101 141 015 137 304 163 236 167 73 016 155 293 135 351 138 216 017 205 363 193 397 158 204 018 279 413 271 368 134 97 019 244 380 227 374 136 147 020 208 308 243 319 100 76 021 212 287 229 313 75 84 022 293 374 330 382 81 52 Average 214.4 322.7 220.2 310.3 108.3 9Θ.1 Medium 209.0 308.0 224.0 322.0 103.0 76,0 Minimum 137.0 258.0 117.0 172.0 31.0 -20.0 Maximum 328.0 413.0 340.0 397.0 199.0 218.0 Standard erros 12.2 10.9 13.6 14.0 9.7 13.4 1C of 95% [189.9; 238.9] [300.9; 344.6] [193; 247.4] [282.3; 338.3] [88.9; 127.8] [63 2; 117] &amp;(%) with respect to the TO 50.5 40.9 % of volunteers with irritating effect 100.0 94.7 P-Value <0.001*** <0.001*** *** significant at level 0.1%; ^significant at level 1%; Significant at level 5% (t-Student test). The time TO was higher on the average than the time Tb for product and control Table 34: Measurements and descriptive statistics of the product Subject TO T3°· T1h T2h 1 min T3h T4h TSh T6h Δ{Τ30 Δ -min- (T1 ΝΤΟ! TO] Δ Δ (T2h- (T3h~ TO} TO) Δ {T4h- ΤΘ) Δ (T5h- ΤΘ) Δ {T8h- T0) 002 325 214 210 204 224 248 248 227 -111 · -115 -121 -101 -77 -77 -98 004 293 323 320 284 309 296 280 311 30 27 -9 16 3 -13 18 005 291 198 191 194 191 207 203 213 -93 -100 -97 -100 -84 -88 -78 006 346 289 232 259 243 262 240 245 -57 -114 -87 -103 -84 -108 -101 007 346 209 202 220 269 208 251 277 -137 -144 -126 -77 -138 -95 -69 008 369 278 269 267 266 250 264 242 -91 -100 -102 -103 -119 -105 -127 009 258 235 192 187 190 186 228 182 -23 -66 -71 -68 -72 -30 -76 010 266 193 190 229 225 227 231 233 -73 -76 -37 -41 -39 -35 -33 012 269 245 212 211 209 226 302 265 -24 -57 -58 -60 -43 33 -4 013 383 276 319 325 320 305 336 350 -107 -64 -58 -63 -78 -47 -33 014 264 149 157 176 178 185 195 195 -115 · -107 -88 -86 -79 -69 -69 015 304 200 214 191 194 204 214 244 -104 -90 -113 -110 -100 -90 -60 016 293 229 192 188 183 207 249 265 -64 -101 -105 -110 -86 -44 -28 017 363 225 191 255 206 248 260 249 -138 -172 -108 -157 -115 -103 -114 018 413 345 311 359 325 336 366 347 -68 -102 -54 -88 -77 -47 -66 019 380 335 312 267 255 316 287 308 -45 -68 -113 -125 -64 -93 -72 020 308 230 241 226 166 247 254 231 -78 -67 -82 -142 -61 -54 -77 WO 2015/172221 46 PCT/BR2015/050058 021 287 191 194 196 176 197 190 225 -96 -93 -91 -111 -90 -97 -62 022 374 340 335 310 328 316 288 290 -34 -39 -64 -46 -58 -86 -84 Average 322.7 247.6 236.0 239.4 234.6 245.8 257.2 257.8 -75.2 -86.7 -83.4 -88.2 -76.9 -65.6 -64.9 Medium 308,0 230,0 212.0 226.0 224.0 247.0 251.0 245,0 -78.0 -93.0 -88.0 -100.0 -78.0 -77.0 -69,0 Minimum 258,0 149.0 157.0 176.0 166.0 185.0 190.0 182.0 -138.0 -172.0 -126.0 -157.0 -138.0 -106.0 -127.0 Maximum 413.0 345.0 335.0 359.0 328.0 336.0 366.0 350.0 30.0 27.0 -9.0 16.0 3.0 33.0 18.0 Standard error 10.9 13.2 12.9 12.0 12.5 10.9 10.5 10.7 9.8 9.6 7.1 9.1 7.2 8.5 8.3 !C of 95% [300.9; [221.2; [210.1; [215.4; [209.5; [224; [236.2;[236.5; [-94.8;[-105.9;[-97.5; [-106.3; 344.61 273.9] 261.9] 263.4] 259.6] 267.7] 278.2] 279.2] -55.5] -67.6] -69.2] -70.1] [-91.3; -62.5] [-82.6; -48.5] [-81.5; -48.3] Δ(%) with respect to TO -23.3 -26.9 -25.8 -27.3 -23.8 -20.3 -20.1
Tabie 35: Measurements and descriptive statistics of the control
Subject TO T3Q- mirs T1h T2h T3h T4h TSh TSh Δ{Τ30 -min- TQ) Δ (T1h- T0) Δ (T2h- T0) Δ (T3h- T0) Δ (T4h- TO) Δ [T5h- TQ) Δ <T6h- ΤΘ) 002 291 194 214 201 216 245 245 241 -97 -77 -90 -75 -46 -46 -50 004 322 327 326 283 301 318 314 297 5 4 -39 -21 -4 -8 -25 005 256 193 178 189 189 189 210 196 -63 -78 -67 -67 -67 -46 -60 006 323 282 242 250 258 248 250 242 -41 -81 -73 -65 -75 -73 -81 007 213 175 181 176 217 198 226 221 -38 -32 -37 4 -15 13 8 008 338 304 297 287 288 267 270 280 -34 -41 -51 -50 -71 -68 -58 009 334 259 231 213 202 176 228 200 -75 -103 -121 -132 -158 -106 -134 010 172 202 166 206 180 200 163 184 30 -6 34 8 28 -9 12 012 285 234 204 232 209 230 271 262 -51 -81 -53 -76 -55 -14 -23 013 364 279 299 329 365 329 349 352 -85 -65 -35 1 -35 -15 -12 014 258 195 205 195 216 185 191 219 -63 -53 -63 -42 -73 -67 -39 015 236 160 151 147 156 212 189 194 -76 -85 -89 -80 -24 -47 -42 016 351 273 292 344 278 257 276 290 -78 -59 -7 -73 -94 -75 -61 017 397 238 218 251 209 257 251 260 -159 -179 -146 -188 -140 -146 -137 018 368 327 267 305 289 272 322 327 -41 -101 -63 -79 -96 -46 -41 019 374 298 290 264 235 329 320 311 -76 -84 -110 -139 -45 -54 -63 020 319 244 274 237 215 259 254 258 -75 -45 -82 -104 -60 -65 -61 021 313 235 235 228 233 248 246 238 -78 -78 -85 -80 -65 -67 -75 022 382 333 322 336 328 312 291 297 -49 -60 -46 -54 -70 -91 -85 Average 310.3 250.1 241.7 245.9 241.3 249.0 256.1 256.3 -60.2 -66.6 -64.4 -69.1 -61.3 -54.2 -54.1 Medium 322.0 244,0 235.0 237.0 217.0 248.0 251,0 258,0 -63.0 -77,0 -63.0 -73.0 -65,0 -54.0 -58.0 Minimum 172.0 160.0 151.0 147,0 156.0 176.0 163.0 184.0 -159.0 -179.0 -146.0 -188.0 -158.0 -146.0 -137.0 Maximum 397.0 333.0 326.0 344.0 365.0 329.0 349.0 352.0 30.0 4.0 34.0 8.0 28.0 13.0 12.0 Standard error 14.0 12.4 12.4 13.0 12.4 11.1 11.3 11.0 9.0 9.0 9.4 11.4 10.0 8.7 9.0 !C of 95% [282.3;[225.3;[216.9; [220; [216.5; [226.7; [233.4; [234.2; 338.3] 274.9] 266.4] 271.8] 266.11 271.31 278.8] 278.3] [-78.3; -42.2] [-86.6; -50.6] [-83.1; -45.7] [-91.9; -46.2] [-81.4; -41.3] [-71.6; -36.8] [-72.1; -36] Δ(%) em reiagao ao TO -19.4 -22.1 -20.7 -22.3 -19.8 -17.5 -17.4 WO 2015/172221 47 PCT/BR2015/050058
Tabie 36: Average and standard error for each treatment per time and for the difference between treatments
Time Product Control Product - Controi Average E.P. Average E.P. Average E.P. TO 322.7 10.9 310.3 14.0 12.4 11.7 TSOmin 247.8 13.2 250.1 12.4 -2.5 6.1 T1h 236.0 12.9 241.7 12.4 -5.7 8.7 T2h 239.4 12.0 245.9 13.0 -6.6 10.1 T3h 234.8 12.5 241.3 12.4 -6.7 8.7 T4h 245.8 10.9 249.0 11.1 -3.2 6.0 T5h 257.2 10.5 256.1 11.3 1.1 6.7 T6h 257.8 10.7 256.3 11.0 1.6 6.2
Table 37: Porcentage of variation in the average with respect to the TO and percentage of volunteers with positive and negative effect
Produto - Controle Time % of variation with respect to TO % of subjects with positive effect % of subjects with negative effect T30min -3.9 63.2 36.8 T1h -4.8 63.2 36.8 T2h -5.1 73.7 21.1 T3h -5.1 68.4 21.1 T4h -4.1 63.2 36.8 T5h -2.9 68.4 31.6 T6h -2.7 63.2 36.8 5
No significant difference was found between the treatments in the times TSOmin, T1h, T4h, T5h and T6h (P-vaiues = 0.138; 0.054; 0.147; 0.250; 0.207, respectively). The product was inferior to the control in the times T2h and T3h (p-values = 0.048; 00.41, respectively). 10 Wherein:
Cm2: square centimeters; G: grams; H: hours;
No,: number; 15 °C; degrees Celsius;
Tx: Time after x hours from application of the product. 6.7 - Conclusion WO 2015/172221 PCT/BR2015/050058 48
After a statistical analysis of the results, one can conclude that the composition of the invention promoted the reduction of the erythema in the times T2h and T3h as compared with the control.

Claims (16)

1. An antiperspirant deodorant cosmetic composition with dermo-calming action characterized by comprising 2-metbyi-5-cyciQhexyipentanoi, aluminum hydrochloride, and cosmetically acceptable adjuvants,
2. The composition according to claim 1, characterized by further containing a conditioning agent and a consistency agent.
3. The composition according to claim 2, characterized in that the conditioning agent is pantenol and the consistency agent is hydroxypropylic starch phosphate.
4. The composition according to any one of claims 1 to 3, characterized in that the cosmetically acceptable adjuvants are selected from the group consisting of emulsifying agent, preserving agent, antioxidant agent, sequestering (or chelating) agent, oil, water and fragrance.
5. The composition according to any one of claims 1 to 4, characterized in that said sequestering agent is disodium EDTA.
6. The composition according to any one of claims 1 to 5, characterized in that said preserving agent is dimethyldimethyihydantoin (DMDM hydantoin).
7. The composition according to any one of claims 1 to 6, characterized in that said antioxidant agent is butyiated hydroxidetoluene (BHT).
8. The composition according to any one of claims 1 to 7, characterized in that said oil is olus oil.
9. The composition according to any one of claims 1 to 7, characterized in that said oil is hydrogenated palm oil.
10. The composition according to any one of claims 1 to 9, characterized by further comprising silica dimethyl sililate and PPG-15 stearyl ether.
11. The composition according to any one of claims 1 to 10, characterized in that said emulsifying agent is selected from the group consisting of steareth-2 and steareth-21.
12. The composition according to any one of claims 1 to 9, characterized by further comprising dicapry! carbonate, cyclopentasyloxane, dimethiconol, magnesium silicate, ceresin wax.
13. The composition according to any one of claims 1 to 9 and 12, characterized in that said emulsifying agent is selected from the group consisting of cetostearyl alcohol and ceteareth-20.
14. The composition according to any one of claims 1 to 11, characterized in that it is in the form of roll-on deodorant.
15. The composition according to any one of claims 1 to 9, 12 and 13, characterized in that it is in the form of a cream deodorant.
16. The composition according to claim 14 or 15, characterized in that it is for after-depilation use.
AU2015258729A 2014-05-16 2015-05-15 Antiperspirant deodorant cosmetic composition having dermo-calming action Abandoned AU2015258729A1 (en)

Applications Claiming Priority (3)

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US14/279,773 2014-05-16
US14/279,773 US20150328099A1 (en) 2014-05-16 2014-05-16 Antitranspirant Deodorant Cosmetic Composition Having Dermo-Calming Action
PCT/BR2015/050058 WO2015172221A1 (en) 2014-05-16 2015-05-15 Antiperspirant deodorant cosmetic composition having dermo-calming action

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FR3027800B1 (en) * 2014-10-29 2018-01-26 L'oreal COMPOSITION BASED ON SEBUM-COATING AND / OR ABSORBENT POWDER AND ALUMINUM SALT
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DE102007035139A1 (en) 2007-07-25 2009-01-29 Symrise Gmbh & Co. Kg 3- (4-hydroxy-3-methoxyphenyl) -1- (4-hydroxyphenyl) -1-propanone and its use as antimicrobial agent
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US20150328099A1 (en) 2015-11-19
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CL2016002919A1 (en) 2017-04-07
EP3142632A1 (en) 2017-03-22

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